Download - Hsp Proteins

Heat Shock Proteins and Molecular Chaperones

Hsp10

Hsp27

Hsp32

Hsp40

Hsp60

Hsp70

Hsp90

Hsp110

Chaperones


· Antibodies · Proteins · ELISA Kits

02


Heat shock proteins are ubiquitously expressed polypeptides whose

expression increases in response to a variety of different metabolic insults.

Despite their designation, most of the heat shock proteins are constitutively

expressed and perform essential functions. Most notable is their role as

molecular chaperones, facilitating the synthesis and folding of proteins

throughout the cell. In addition, heat shock proteins have been shown to

participate in protein assembly, secretion, trafficking, protein degradation,

and the regulation of transcription factors and protein kinases. Increased

levels of the heat shock proteins after stress plays a central role in cellular

homeostasis.

Assay Designs is committed to providing scientists with reliable tools for

scientific discovery. Our merger in 2005 with Stressgen Bioreagents has

broadened our product offering to include an extensive collection of heat

shock protein related products including ELISA kits, antibodies, recombinant

proteins, and reagents. We are pleased to add the high quality products

generated by over 15 years of Stressgen research into our product line, and

are dedicated to the further development and manufacturing of novel user-

friendly heat shock protein related products. Assay Designs aims to Simplify

Your Science® by offering this guide to the heat shock protein families, and

the products we offer to advance research in this existing field.

Hsp10 ....................................3

Hsp27 ....................................3

Hsp32 ....................................5

Hsp40 and the DnaJ Family ...7

Hsp60 and GroEL ..................9

Hsp70 and DnaK .................11

Hsp90 ..................................13

Hsp110 ................................15

Chaperones & Others .........16

Hsp27 Review .....................20

Hsp70 Review .....................22

Hsp90 Review .....................24

References ..........................26

Species:H: humanM: mouseR: ratB: bovineC: chickenD: drosophilaY: yeast

Applications:WB: western blotIP: immunoprecipitationICC: immunocytochemistryIHC: immunohistochemistryF: flow cytometry

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Hsp10

Hsp10, also known as Chaperonin 10 (Cpn10), is the ~10

kDa mammalian equivalent of the bacterial GroES gene

product. Hsp10 exists in vivo as an oligomer and interacts

with Hsp60, the mammalian homolog of the bacterial

GroEL protein. Together the Hsp10/Hsp60 chaperonin pre-

sent within mitochondria facilitates the folding of newly

synthesized proteins and may participate in the refolding

of proteins damaged after stress. In plants, a similar chape-

ronin system operates within chloroplasts and is referred

Assay Designs (Stressgen) Products

Cat. No. Product Description Species Application

SPA-110 Hsp10 (Cpn10) Polyclonal Antibody H, M, R, X WB, IP

SPA-210 GroES Polyclonal Antibody E.coli WB, IP

SPP-620 GroES Recombinant Protein E.coli

Official Symbol Name SynonymsEntrez Gene ID Biological Function

Tissue Distribution

Cellular Distribution

HSPE1 Heat Shock 10kDa Protein 1 (Chap-eronin 10)

CPN10, GROES, HSP10

3336 Caspase activation, Chaperone binding, Protein folding Broad Mitochondria Chloroplasts

Assay Designs (Stressgen) ProductsCat. No. Product Description Species Application

EKS-500 Hsp27 ELISA Kit H

SPA-796 Hsp20 Polyclonal Antibody H, M, R WB

SPA-801 Hsp25 Polyclonal Antibody M, R WB, IP, ICC, IHC

SPA-803 Hsp27 Polyclonal Antibody H WB, IP, ICC, IHC

SPA-800 Hsp27 Monoclonal Antibody (G3.1) H, M, R WB, IP, ICC, IHC

SPA-525 Hsp27 (phospho-Ser15) Polyclonal Antibody H, M, R WB

SPA-523 Hsp27 (phospho-Ser78) Polyclonal Antibody H, M, R WB, IP

SPA-524 Hsp27 (phospho-Ser82) Polyclonal Antibody H, R WB, IP

905-642 Hsp27 (phospho-Ser82) Monoclonal Antibody H, M, R WB

SPA-800FI Hsp27 Monoclonal Antibody, FITC Conjugate H, M, R F, IF

SPA-800B Hsp27 Monoclonal Antibody, Biotin Conjugate H, M, R

SPA-221 a A Crystallin Polyclonal Antibody B WB, IP

SPA-222 a B Crystallin Monoclonal Antibody H, M, R, B, C WB, ICC, IHC

SPA-223 a B Crystallin Polyclonal Antibody H, M, R, B WB, IP

SPA-224 a A/B Crystallin Polyclonal Antibody B WB

SPA-225 a B Crystallin (phospho-Ser19) Polyclonal Antibody H, M, B WB, IP

SPA-226 a B Crystallin (phospho-Ser45) Polyclonal Antibody H, M, R, B, C, X WB, IP

SPA-227 a B Crystallin (phospho-Ser59) Polyclonal Antibody M, R, B WB, IP

SPA-230 b Crystallin Monoclonal Antibody (3H92) B WB

NSP-510 Hsp25 Recombinant Protein M

SPP-715 Hsp27 Recombinant Protein H

ESP-715 Hsp27 Recombinant Protein - Low Endotoxin H

SPP-226 a A Crystallin Native Protein B

SPP-227 a B Crystallin Native Protein B

SPP-225 a A/B Crystallin Native Protein B

to as the Rubisco-Binding protein. Finally, in bacteria GroEL and

GroES participate in the folding and assembly of numerous pro-

teins.

Hsp27 Hsp27 Review on page 20

Hsp27 (sometimes referred to as

Hsp20, Hsp25, Hsp28 or the low

molecular weight heat shock prote-

in) is homologous to the a Crystallin

proteins. Both families of proteins

are characterized by their oligomeric

structure and are thought to func-

tion as ATP-independent chaperones.

Hsp27 structure/function is thought

to be modulated by phosphorylation

mediated by different protein kinases.

In addition to their chaperone role,

Hsp27 and aB-Crystallin have been

shown to mediate structural integrity

and membrane stability, affecting actin

polymerization, intermediate filament

organization, apoptosis, and invasive

potential. Evidence suggests altered

expression of small heat shock proteins

is implicated in the pathogenesis of

human diseases including cancer, ca-

taracts, neurodegenerative disorders,

and cardiovascular disease.

03

Hsp27 (continued)

Official Symbol Name Synonyms

Entrez Gene ID Biological Function

Tissue Distribution

Cellular Localization

Human Diseases

CRYAA Crystallin, a A CRYA1, HSPB4 1409 Structural component of eye, Protein Folding

Eye Lens Cytoplasm Cataracts

CRYAB Crystallin, a B CRYA2, HSPB5 1410 Structural component of eye, Protein Folding, Muscle contraction, Muscle development, Protein folding, Receptor mediated signaling, Visual perception

Broad Contrac-tile fibers, Cytoplasm, Nucleus, Plasma membrane

Cataracts, Mul-tiple Sclerosis

HSPB1 Heat Shock 27kDa Protein 1

HSP27, Hsp25 3315 Anti-apoptosis, Cell motility, Protein folding

Broadly Cytoplasm Nucleus, Plasma Membrane

Charcot-Marie-Tooth disease, axonal, type 2F.Neuropathy, distal hereditary motor


MKBP 3316 Enzyme Activator, Protein Folding, Somatic Muscle Development

Heart, Skeletal Muscle, Skin

Cytoplasm, Nucleus


HSPL27 8988 Protein Folding Muscle

HSPB6 Heat Shock Pro-tein, a-Crystallin-related, B6

Hsp20 126393 Structural component of eye, Protein Folding, Muscle Contraction

Muscle, Ovary Actin cytoskel-eton

HSPB7 Heat Shock 27kDa Protein family, member 7 (cardio-vascular)

cvHSP 27129 Protein Folding, Muscle Contraction Cardiac, Connective, Skeletal

Contractile Fibers


H11; E2IG1; HSP22 26353 Kinase Activity, Transferase Activity, Protein Folding

Broadly Cytoplasm, Plasma Mem-brane

Charcot-Marie-Tooth disease type 2L. Hereditary mo-tor neuropathy type II

HSPB9 Heat Shock Pro-tein, a-Crystallin-related, B9

94086 Protein Folding Testes Nucleus, Cyto-plasm

ODF1 Outer dense fiber of sperm tails 1

HSPB10, ODFP, SODF

4956 Structural activity, Cell differentiation, Spermatogenesis

Testes Cytoplasm

Hsp27 (phospho-Ser82) Polyclonal Antibody (Cat. No. SPA-524)Confocal immunofluorescent staining of Hela

cells using Phospho-Hsp (Ser82) Polyclonal Anti-

body (Cat. No. SPA-524; green) (A).

Blue pseudocolor fluorescent dye DRAQ5 was

used to stain cell nuclei (B).

In (C) the two images are overlapped.

A B C

04 H: human, M: mouse, R: rat, B: bovine, C: chicken, D: drosophila, Y: yeast

Hsp32 (Heme Qxygenase)

Heme oxygenase or Hsp32 is an es-

sential component in the catabolism

of heme, catalyzing the first step in

the degradation of heme to bilirubin.

Heme oxygenase consists of at least

three isoforms: stress inducible HO-1,

and constitutively expressed HO-2

and HO-3. Induction of HO-1 occurs

in response to heat shock, oxidative

stress, thiol reacting reagents, heavy

metals, inflammatory mediators and

certain growth factors. The majo-

rity of the protein is localized to

the endoplasmic reticulum, but the

protein can also be present at the

plasma membrane and mitochond-

ria. The products produced by heme

oxygenase have important physiolo-

gical effects: carbon monoxide is a

potent vasodilator; biliverdin and its product bilirubin are antioxidants; and the released iron can increase oxidative stress if not

effectively reutilized. Modulation of HO expression may be useful for protection against atherosclerotic disease, oxidative stress,

coronary ischemia, hypertension and certain neurodegenerative diseases.



Tissue Distribution


HMOX1 Heme Oxygenase 1 HO-1 3162 Breakdown of heme, protection against oxidative stress, Ion binding, NFkB signaling

Broad Endoplasmic reticulum

HMOX2 Heme Oxygenase 2 HO-2 3163 Breakdown of heme, protection against oxidative stress, Electron carrier, Ion binding


Heme-Oxygenase-1 (Hsp32) Monoclonal Antibody (Cat. No. OSA-111)Human lung carcinoma tissue was immunohistochemically

stained using Heme-Oxygenase-1 Monoclonal Antibody (clone

HO-1-2) at a dilution of 1:50. Another Heme-Oxygenase-1 mo-

noclonal (clone HO-1-1, Cat. No. OSA-110) (1:50) was negative

for staining the same lung cancer tissue.

Cat. No. Product Description Species Application

EKS-800 HO-1 (Hsp32; Human) ELISA Kit H

EKS-810 HO-1 (Hsp32; Rat) ELISA Kit R

SPA-895 HO-1 (Hsp32) Polyclonal Antibody H, M, R WB, IP, ICC, IHC, F

SPA-896 HO-1 (Hsp32) Polyclonal Antibody H, M, R WB, IP, ICC, IHC

OSA-150 HO-1 (Hsp32) Polyclonal Antibody H, M, R WB, IP

OSA-110 HO-1 (Hsp32) Monoclonal Antibody (HO-1-1) H, M, R WB, F

OSA-111 HO-1 (Hsp32) Monoclonal Antibody (HO-1-2) H, M, R WB, IHC, F

OSA-111FI HO-1 (Hsp32) Monoclonal Antibody-FITC Conjugate H, M, R F, IF

OSA-111B HO-1 (Hsp32) Monoclonal Antibody-Biotin Conjugate H, M, R

OSA-200 HO-2 Polyclonal Antibody H, M, R WB

SPA-897 HO-2 Polyclonal Antibody H, M, R, C WB, IP, ICC

SPP-730 HO-1 (Hsp32) Recombinant Protein R

SPP-732 HO-1 (Hsp32) Recombinant Protein H

NSP-550 HO-2 Recombinant Protein H

05WB: western blot, IP: immunoprecipitation, ICC: immunocytochemistry, IHC: immunohistochemistry, F: flow cytometry

Hsp32 (continued)

Heme-Oxygenase-1 (Hsp32) Monoclonal Antibody (Cat. No. OSA-110)Human lung cancer A2 cells were analyzed by flow cytometry

using isotype control antibody (left) or Heme-Oxygenase-1

Monoclonal Antibody (clone HO-1-1; right) at a final concen-

tration of 10µg/mL.

Heme Oxygenase 1 (Hsp32)Crystal structure of human Heme Oxygenase-1 in complex with

its substrate Heme (Schuller, D.J. et al. 2002).

06

Hsp40 and the DnaJ Family

Mammalian Hsp40, present within the cytosol, is one

of a number of family members closely related to

the DnaJ protein first described in E.coli. Hsp40/DnaJ

family members work in concert with the Hsp70/DnaK

proteins, facilitating the hydrolysis of ATP to ADP and

thereby helping to lock in the binding of the Hsp70

chaperone to its protein substrate. Consequently,

each of the different members of the Hsp70 family in

eukaryotes require a specific DnaJ homolog for their

chaperone activity. More than 20 genes encoding DnaJ-

related proteins have been identified in yeast. In animal cells the Hsp40 family of proteins display a broad tissue distribution with indi-

vidual members present within most intracellular compartments. Assay Designs currently provides both the DnaJ and Hsp40 proteins in

purified form, along with a number of antibodies specific for each protein. New products targeting other members of the DnaJ/Hsp40

family are expected in the near future.



Tissue Distribution


DNAJA1 DnaJ (Hsp40) homolog, subfamily A, member 1

DJ-2; DjA1; HDJ2; HSDJ; HSJ2; HSPF4; hDJ-2

3301 Protein binding, Protein folding, LDL receptor binding, Ion binding

Broadly CytoplasmNucleusNucleolusGolgi


CPR3; DJA2; DNAJ; DNJ3; RDJ2; HIRIP4

10294 Protein binding, Ion binding, Cell cycle, Protein Folding

Broadly CytoplasmNucleusMitochondrion


TID1, hTid-1 9093 GTPase activity, Ion Binding, GPCR Signaling, Protein folding, Protein folding, Regulation of apoptosis

Broad Mitochondrion


MST104; MSTP104; PRO1472

55466 Protein binding, Ion binding, Protein folding

Broad

DNAJA5 DnaJ homology subfam-ily A, member 5

GS3 protein 134218 Protein binding, Nucleic acid binding, Ion binding, Protein folding

Broad CytoplasmNucleus

DNAJB1 DnaJ (Hsp40) homolog, subfamily B, member 1

Hdj1; HSPF1; Hsp40 3337 Protein binding, Protein Folding Broad Nucleus


HSJ1; HSPF3 3300 Protein binding, Protein folding Broad CytoplasmNucleus


DjB4; HLJ1; DNAJW 11080 Protein binding, Protein folding Broad


Hsc40 25822 Protein binding, Protein folding Broad


MRJ; HSJ2; HHDJ1; HSJ-2; MSJ-1

10049 Protein binding, Protein folding Broad CytoplasmNucleus


HSC3 150353 Protein Binding, Protein folding Broad


MGC33884 165721 Protein binding, Protein folding


MDG1; ERdj4 4189 Chaperone, Protein folding, activity, Protein binding

Broad CytoplasmEndoplasmic reticulumNucleolus Nucleus


EDJ; ERj3; HEDJ; hDj9; ABBP2; ERdj3; ABBP-2

51726 Protein binding, Protein folding Broad CytoplasmEndoplasmic reticulumNucleus

Assay Designs (Stressgen) ProductsCat. No. Product Description Species Applications

SPA-400 Hsp40 Polyclonal Antibody H, M, R, C, X WB, IP, ICC, IHC

SPA-450 Hsp40 Monoclonal Antibody (2E1) H, M, R WB, IP

SPA-410 DnaJ Polyclonal Antibody E. coli WB, IP

SPP-400 Hsp40 Recombinant Protein H

SPP-640 Active DnaJ Recombinant Protein E. coli

07datasheet: www.biomol.de www.antibodyworld.com

Hsp40 (continued)



Tissue Distribution



DJ10 54788 Protein binding, Protein folding Plasma mem-brane

DNAJB13 DnaJ (Hsp40) related, subfamily B, member 13

TSARG5; TSARG6 374407 Protein binding, Apoptosis, Protein folding, Spermatogenesis

Testis


79982 Protein binding, Protein folding

DNAJC1 DnaJ (Hsp40) homolog, subfamily C, member 1

HTJ1; ERdj1; DNAJL1 64215 ATPase activation, Protein folding, Chaperone folding, DNA binding

Endoplasmic reticulumMembraneMicrosomeNucleus


Zrf1; Zrf2; MIDA1 22791 DNA binding, Cell cycle, Protein binding, DNA replication, Protein folding, Transcription

Nucleus


P58; HP58; PRKRI; P58IPK 5611 Protein binding, Protein folding, Kinase inhibitor, Defense

Broad Cytoplasm


HSPF2; MCG18; DANJC4 3338 Protein binding, Protein folding Membrane


CSP 80331 Protein binding, Protein folding Pituitary Gland Membrane

DNAJC5B DnaJ (Hsp40) homolog, subfamily C, member 5 b

CSP-b 85479 Protein binding, Protein folding

DNAJC5G DnaJ (Hsp40) homolog, subfamily C, member 5 g

CSP-g 285126 Protein binding, Protein folding Membrane


DJC6 9829 Protein binding, Signal transduction, Hydrolase activity, Protein folding, Phosphatase activity

Broad Nucleus


TPR2; TTC2; DANJC7 7266 Protein binding, Protein folding


SPF31; HSPC331 22826 Protein binding, Protein folding Nucleolus


JDD1; SB73 23234 Protein binding, Protein folding Broad


JPDI; ERdj5 54431 Protein binding, Redox homeostasis, Protein folding

Broad Endoplasmic Reticulum


55735 Protein binding, Protein folding Mitochondrion


JDP1 56521 Protein binding , Protein folding Broad


RME8 23317 Protein binding, Protein folding Broad Endosome


DNAJ; HDJ3; LIP6 85406 Protein binding, Protein folding Broad Endoplasmic reticulum


MCJ; HSD18; DNAJD1 29103 Protein binding, Protein folding Broad


23341 Protein binding, Protein folding Broad Membrane


55192 RNA binding, Protein folding, Protein binding


202052 Protein binding, Protein folding Membrane


TIM14; TIMM14 131118 Protein binding, Protein folding, Protein transport

MembraneMitochondrion

DNAJC20 HscB iron-sulfur cluster co-chaperone homolog (E. coli)

HSCB, JAC1; HSC20 150274 Chaperone binding, Protein binding, Protein folding

Broad Mitochondrion

HSCB HscB iron-sulfur cluster co-chaperone homolog (E. coli)

DNAJC20 150274


Hsp47 Monoclonal Antibody (Cat. No. SPA-470)Human breast cancer tissue was immunohistochemically

stained using Hsp47 Monoclonal Antibody (clone M16.10A1) at

a dilution of 1:50.

Members of the Hsp60 (eukaryotes) and Gro-

EL (bacterial) family of heat shock proteins

are some of the best characterized molecular

chaperones. Bacterial GroEL, named because of

its essential role in bacteriophage growth, exists

as a large homo-oligomeric complex which re-

cognizes and binds to unfolded polypeptides. In

combination with its particular co-factor (Hsp10

in eukaryotes, GroES in bacteria) the Hsp60/

GroEL proteins bind newly synthesized polypep-

tides and facilitate their folding to the native

state via one or more rounds of ATP hydrolysis.

Mammalian Hsp60 is localized within mito-

chondria, while a related form of the protein

termed Rubisco-binding protein operates within

plant chloroplasts. Finally, within the eukaryotic

cytosol, related proteins referred to as CCT or

TRIC make a hetero-oligomeric structure and

have been shown to similarly bind select protein

substrates and facilitate their folding and/or

higher order assembly. Oftentimes the GroEL/ES

or Hsp60/Hsp10 protein folding machineries

are referred to as the chaperonins. In vitro as

well as in vivo chaperonins, either alone or with

other chaperones and ATP, have been shown to

orchestrate the re-folding of partially denatured

proteins. In addition to their prominent role as

molecular chaperones members of the GroEL

and Hsp60 families have long been recognized as


EKS-600 Hsp60 ELISA Kit (measures protein) H

EKS-650 Hsp60 ELISA Kit (measures antibodies) H

SPA-807 Hsp60 Monoclonal Antibody (LK-2) H, M, R, C, Y WB, IHC, F

SPA-806 Hsp60 Monoclonal Antibody (LK-1) H, M, R, C, X WB, IP, F

SPA-829 Hsp60 Monoclonal Antibody (11-13) H, M, R, D WB, IP, IHC, F

SPA-828 Hsp60 Goat Polyclonal Antibody H, M, R, C, X WB, IP

SPA-881 Hsp65 Monoclonal Antibody (3F7) H, M, R, D WB

SPS-870 GroEL Monoclonal Antibody (9A1/2) E. coli WB, IP

SPS-875 GroEL Polyclonal Antibody H, M, R, Y, E. coli WB

SPA-110 Hsp10 (Cpn10) Polyclonal Antibody H,,M, R, X W, IP

SPA-210 GroES Polyclonal Antibody E. coli W, IP

CTA-123 TCP-1a Monoclonal Antibody (23c) M, R W, IP, ICC

CTA-191 TCP-1a Monoclonal Antibody (91a) H, M, R, D, Y WB, IP, F

CTA-202 TCP-1b Monoclonal Antibody H, M, R, C WB

ESP-540 Active Hsp60 Recombinant Protein

(Low Endotoxin)

H

NSP-540 Active Human Hsp60 Recombinant Protein H

ESP-741 Active Mouse Hsp60 Recombinant Protein

(Low Endotoxin)

M

SPP-741 Hsp60 Recombinant Protein M

SPP-742 Hsp60 Recombinant Protein R

NSP-581 Hsp65 Recombinant Protein Mycobacterim

SPP-610 Active GroEL Recombinant Protein E. coli

SPP-620 GroES Recombinant Protein E. coli

Hsp60 and GroEL: the “Chaperonins”


Hsp60 (continued)



Tissue Distribution


Human Diseases

HSPD1 Heat Shock 60kDa Protein 1 (chap-eronin)

CPN60; GROEL; HSP60; HSP65; SPG13; HuCHA60

3329 Protein folding, Nucleotide binding, Protein import, Regulation of apoptosis

Broad MitochondrionCytoplasm

Spastic paraplegia

Hsp60 Monoclonal Antibody (Cat. No. SPA-807) Human colon cancer tissue was immunohistochemically stained

using Hsp60 Monoclonal Antibody (clone LK-2) at a dilution of

1:50.

Hsp60 Monoclonal Antibody (Cat. No. SPA-829)Human hepatoma tissue was immunohistochemically stained

using Hsp60 Monoclonal Antibody (clone LK-1) at a dilution

of 1:50. Another Hsp60 monoclonal (clone 11-13, Cat. No.

SPA-806) (1:50) was negative for staining the same hepatoma

tissue.

Hsp60 Monoclonal Antibody (Cat. No. SPA-806)Human hepatoma QGY cells were analyzed by flow cytometry using isotype control antibody (left) or Hsp60 Monoclonal

Antibody (clone LK-1; right) at a final concentration of 10µg/mL.

highly immunogenic proteins and consequently have attracted

much attention from immunologists. Assay Designs offers a

comprehensive panel of both purified chaperonin proteins

isolated from different sources along with antibodies capable

of discerning the different family members.

10

Hsp70 and DnaK Hsp70 Review on page 22

The Hsp70 family of heat shock proteins contains multiple ho-

mologues ranging in size from 66kDa to 78kDa. These proteins

include cognate members which are found within major in-

tracellular compartments, and highly inducible isoforms which

are predominantly cytoplasmic or nuclear in distribution. All

Hsp70 family members contain a highly conserved N-terminal

ATPase domain, as well as a conserved hydrophobic peptide

binding domain (PBD) and more variable a-helical “cap” do-

main. Activation of Hsp70 is coordinated by binding of ATP at

the N-terminus, causing a conformational change that opens

the cap, allowing interaction of the PBD with a wide variety

of client proteins in their unfolded, misfolded, or denatured

state. Hsp70 ATPase activity is influenced by association with

specific co-chaperone molecules, including Hsp40, Hip, Hop,

Hup, Hap, and CHIP. These co-chaperones cooperate with

Hsp70 to fold newly synthesized proteins, re-fold misfolded or

denatured proteins, coordinate trafficking of proteins across

cellular membranes, disassemble clathrin-coated vesicles,

inhibit protein aggregation, and target the degradation of

proteins via the proteasomal pathway. Elevated levels of Hsp70

have been associated with inhibition of apoptosis, and clinical

correlations between Hsp70 expression and poor cellular diffe-

rentiation, increased lymph node metastasis, chemoresistance,

and poor clinical outcome indicate Hsp70 may be of use in the

diagnosis, prognosis, and treatment of human malignancy.


EKS-700 Hsp70 ELISA Kit (assay protein) H, M, R

EKS-750 Hsp70 ELISA Kit (assay antibodies) H

EKS-725 Hsp70B’ ELISA Kit (assay protein) H

SPA-810 Hsp70 (Hsp72) Monoclonal Antibody (C92F3A-5) H, M, R, C, D WB, IHC, F

SPA-810FI Hsp70 (Hsp72) Monoclonal Antibody, FITC Conjugate H, M, R, C, D

SPA-810B Hsp70 (Hsp72) Monoclonal Antibody, Biotin Conjugate H, M, R, C, D

SPA-812 Hsp70 (Hsp72) Polyclonal Antibody H, M, R, F WB, IP, ICC, IHC

SPA-811 Hsp70 (Hsp72) Polyclonal Antibody H, M, R WB

SPA-820 Hsp70/Hsc70 Monoclonal Antibody (N27F3-4) H, M, R, C, X WB, F

SPA-822 Hsp70/Hsc70 Monoclonal Antibody (BB70) H, M, R, C, X WB, IHC, F

SPA-757 Hsp70/Hsc70 Polyclonal Antibody H, M, R, C, Y WB, IP

SPA-815 Hsc70 (Hsp73) Rat Monoclonal Antibody (1B5) H, M, R, C WB, IP, ICC, IHC, F

SPA-816 Hsc70 (Hsp73) Polyclonal Antibody H, M, R WB, ICC, IHC

SPA-756 Hsp70B’ Polyclonal Antibody H WB, IP

SPA-754 Hsp70B’ Monoclonal Antibody (175f) H WB

SPA-766 Hip Polyclonal Antibody H, M, R, B WB

SRA-1500 HOP (p60) Monoclonal Antibody (DS14F5) H, M, R, C, X WB, IP

SPS-825 Grp75 Monoclonal Antibody (30A5) H, M, R, C, D, X WB, IHC

SPA-826 Grp78 (BiP) Polyclonal Antibody M, R, X WB, IP, ICC, IHC

NSP-555 Active Hsp70 (Hsp72) Recombinant Protein H

ESP-555 Active Hsp70 Recombinant Protein (Low Endotoxin) H

SPP-758 Active Hsp70 (Hsp72) Recombinant Protein R

SPP-751 Active Hsc70 (Hsp73) Recombinant Protein B

SPP-752 Active Hsc70 (Hsp73) Recombinant Protein,

ATPase fragment

B

ESP-502 Active Hsp70-A2 Recombinant Protein

(Low Endotoxin)

M

SPP-762 Hsp70B’ Recombinant Protein H

SPP-767 Hip Recombinant Protein R

SRP-1510 HOP (p60) Recombinant Protein H

SPP-765 Grp78 (BiP) Recombinant Protein Hamster


Hsp70 (continued)



Tissue Distribution


Human Diseases

HSPA1A Heat Shock 70kDa Protein 1A

HSP72, HSPA1, HSPA1B, HSP70-1

3303 Nucleotide binding, Protein folding

Broadly Cytoplasm, Nucleolus

Alzheimer’s, Ankylosing spondylitis, Asthma, Chronic obstructive pulmo-nary , Multiple sclerosis, Parkinson’s disease, Restenosis, Schizophrenia, Tuberculosis

HSPA1B Heat Shock 70kDa Protein 1B

HSP70-2 3304 Nucleotide binding, Protien folding, Regulation of apoptosis

Broad? Cytoplasm, Endoplasmic reticulum, Mitochondrion Nucleus

Asthma, Alzheimer’s, Obesity, Chronic obstructive pulmonary, Crohn’s disease, Diabetes (type 1 & 2), Hypothyroid-ism, Multiple, Pancreatitis, Parkinson’s disease, Schizophrenia, Sclerosis, Restenosis

HSPA1L Heat Shock 70kDa Protein 1-like

Hum70t, HSP70-HOM

3305 Nucleotide binding, DNA repair, Protein fold-ing, Telomere maintenance

Broad? Cytoplasm, Nucleus

Chronic obstructive pulmonary disease, Graft vs. Host disease, Hypothyroidism, Multiple sclerosis, Parkinson’s disease, Restenosis, Schizophrenia, Septic shock, Storke

HSPA2 Heat Shock 70kDa Protein 2

3306 Nucleotide binding, Protein folding, Spermatogenesis

Broad Nucleus, Cytoplasm, Nucleolus

Alzheimer’s, Crohn’s, Sepsis


RY, APG-2, Hsp70, Hsp70RY, HS24/P52


Broad Cytoplasm Preterm delivery, Carotid Plaques

HSPA5 Heat Shock 70kDa Protein 5 (glucose-regu-lated protein, 78kDa)

BIP, MIF2, GRP78

3309 Nucleotide binding, Apoptosis, Caspase regu-lation, Protein binding, Ribosome binding

Broad Endoplasmic Reticulum, Plasma Mem-brane, Cytoplasm, Nucleolus,

Bipolar disease, Schizophrenia

HSPA6 Heat Shock 70kDa Protein 6 (HSP70B’)


Nucleus

HSPA7 Heat Shock 70kDa Protein 7 (HSP70B)

HSP70B 3311 Nucleotide binding, rotein folding


LAP1, HSC54, HSC70, HSC71, HSP71, HSP73, NIP71, HSPA10

3312 Nucleotide binding, Protein folding, ATPase activity

Broad Cytoplasm, Nucleus

Cystic Fibrosis, Lung cancer

HSPA9 Heat Shock 70kDa Protein 9 (Mortalin)

CSA, MOT, MOT2, GRP75, HSPA9, PBP74, Mot-2

3313 Nucleotide binding, Protein folding, Regulation of apoptosis

CytoplasmMitochondria


HSP70-4; HSP70L1

51182

Hsp70Substrate binding domain of Hsp70 in complex with a substrate peptide.

Science (1996) 272(5268):1606-1614.

Hsp70 Monoclonal Antibody (Cat. No. SPA-810) Human colon cancer tissue was immunohisto-

chemically stained using Hsp70 Monoclonal

Antibody (clone C92F3A-5) at a dilution of 1:50.


Hsp90 Hsp90 Review on page 24

The 90kDa molecular chaperone family comprises several

proteins including the 90 kDa heat shock protein Hsp90 and

the 94kDa glucose-regulated protein grp94, which are major

molecular chaperones of the cytosol and endoplasmic reticu-

lum. In mammalian cells there are at least two Hsp90 isoforms,

Hsp90a and Hsp90b, which are encoded by separate genes. All

known members of the Hsp90 protein family are highly conser-

ved, especially in the N-terminal and C-terminal regions which

contain independent chaperone sites with different client

protein specificity. Hsp90 is part of the cell’s network of cha-

perones that regulate protein folding and assembly, requiring

both ATP and co-chaperones (e.g. Hsp70, Hsp40, Hip/Hop, p23,

and Aha1) for function. Inhibition of the Hsp90 protein folding

machinery targets client proteins for ubiquitin-mediated

proteolysis. Hsp90 is also a necessary component of fundamen-

tal cellular processes such as hormone signaling, cell growth,

and differentiation through its binding of client proteins such

as ErbB2/Her-2, Akt, Raf, CDK1, and CDK4. In addition to its

homeostatic and stress induced roles in protein folding, grp94

can function in the intracellular trafficking of peptides from

the extracellular space to the MHC class I antigen processing

pathway of antigen presenting cells. Strategies seeking to dis-

rupt Hsp90 activation of key pro-survival pathways hold promi-

se as either direct or adjuvant therapies for cancers displaying

altered Hsp90 expression.


EKS-895 Hsp90a ELISA kit H

SPA-830 Hsp90 Monoclonal Antibody (AC88) H, M, R, C WB, IP, ICC, IHC, F

SPA-835 Hsp90 Rat Monoclonal Antibody (16F1) H, M, R, C, D WB, IP, ICC, IHC

SPA-845 Hsp90 Rat Monoclonal Antibody (2D12) H, M, R, C WB, IP

SPA-846 Hsp90 Polyclonal Antibody H, M, R, C WB

SPS-771 Hsp90a Polyclonal Antibody H, M, R, C, X WB, IP

SPA-840 Hsp90a Rat Monoclonal Antibody (9D2) H, C WB, IHC, F

SPA-843 Hsp90b Monoclonal Antibody (K3701) H, M, R WB, F

SPA-842 Hsp90b Monoclonal Antibody (K3705) H, M, R, C WB, IHC

SRA-1400 FKBP-59 (Hsp56, p59) Monoclonal Antibody H, M, R WB, IP, ICC, IHC

SPA-670 p23 Polyclonal Antibody H, M, R WB

SPP-776 Hsp90a Recombinant Protein H

SPP-770 Hsp90 Native Protein H

SPP-670 p23 Recombinant Protein H

HPK-102 Geldanamycin

HPK-101 17-AAG



Tissue Distribution


Human Diseases

HSP90AA1 Heat Shock Protein 90kDa a (cytosolic), class A member

HSPN; LAP2; HSP86; HSPC1; HSPCA; Hsp89; Hsp90; HSP90A; HSP90N; HSPCAL1; HSPCAL4

3320 Nucleotide binding, Protein folding, Protein dimerization, Signal transduction

Broadly Cytoplasm, Nucleus

HSP90AA2 Heat Shock Protein 90kDa a (cytosolic), class A member 2

HSP90ALPHA, HSPCA, HSPCAL3


HSP90AB1 Heat Shock Protein 90kDa a (cytosolic), class B member 1

HSPC2; HSPCB; D6S182; HSP90B; FLJ26984; HSP90-BETA


Broad Cytoplasm

HSP90B1 Heat Shock Protein 90kDa b (Grp94), member 1

GP96; GRP94 7184 Ion binding, Anti-apopto-sis, Nucleotide binding, Ion sequestration , Protein folding, Protein transport


Ischemic neuro-nal cell death


Hsp90 (continued)

Hsp90a Monoclonal Antibody (Cat. No. SPA-840) Human colon cancer tissue was immunohistochemically stained

using Hsp90a monoclonal antibody (clone 9D2) at a dilution of

1:50.

Hsp90b Monoclonal Antibody (Cat. No. SPA-842)Human breast cancer tissue was immunohistochemically

stained using Hsp90b monoclonal antibody (clone K3705) at a

dilution of 1:50.

Hsp90Crystal structure of an Hsp90-Sba1 closed chaperone complex.

Nature (2006) 440(7087):1013-1017.

14

Hsp90a Monoclonal Antibody (Cat. No. SPA-840) Human colon cancer Coca-2 cells were analyzed by flow cytometry using isotype control antibody (left) or Hsp90a monoclonal

antibody (clone 9D2; right) at a final concentration of 10µg/mL.

Hsp110 belongs to a family of large stress proteins referred

to as the Hsp110/SSE (yeast stress seventy) family. Mammalian

Hsp110 shares approximately 30% amino acid identity with its

distant relative Hsp70, primarily in the conserved ATP-binding

domain. Hsp110 is one of the three or four most abundant

Hsps in mammalian tissue, with the highest constitutive ex-

pression in the brain. Functionally, Hsp110 appears to complex

with other chaperones (predominantly Hsp70 and Hsp25) to

maintain and repair protein folding. Hsp110 is more efficient

than Hsp70 in conferring heat resistance, and has been shown

to possess RNA-binding properties via the N-terminal ATP-

binding domain. Due to the inherent efficiency of Hsp110 in

binding peptide, the molecule has been utilized extensively as

an immunoadjuvant to deliver known tumor antigens to an-

tigen presenting cells, generating antigen-specific innate and

adaptive anti-tumor responses.



Tissue Distribution


Human Diseases

HSPH1 Heat Shock 105kDa/110kDa Protein 1

HSP105, HSP105A, HSP105B

10808 Nucleotide binding, Protein binding

Protein folding Broad Cytoplasm


SPA-1101 Hsp110 Polyclonal Antibody H, M, R, B, Y WB, IP

SPA-1103 Hsp110 Polyclonal Antibody H, M, R, B, X WB

Hsp110


Chaperones & Others

The homeostatic process of protein folding and the protective functions of the protein folding machinery in stress-induced conditions (i.e. heat, starvation, oxidation) are dependent on heat shock proteins, as well as a diverse group of co-chape-rones and transcriptional regulators. These molecules inclu-de the Hsp70 co-chaperones HIP and HOP, the ER resident chaperones Calnexin and Calreticulin, and Protein Disulfide-

Isomerase (PDI). ER-resident chaperones are folded in the ER, and retained via their KDEL peptide motif which is bound by the KDEL receptor (Erd2p). Together with the Hsps, these molecules participate in proper glycoprotein folding, prevent premature oligomerization of nascent proteins, regulate Hsp co-chaperone substrate specificity, and promote the rearrange-ment of disulphide bonds in the secretory pathway.

Assay Designs (Stressgen) ProductsCat. No. Product Description Species Application

SPA-860 Calnexin Polyclonal Antibody H, M, R WB

SPA-865 Calnexin Polyclonal Antibody H, M, R, C, X WB, IP, ICC

SPA-600 Calreticulin Polyclonal Antibody H, M, R WB, IP, ICC, IHC

SPA-601 Calreticulin Monoclonal Antibody H WB, IP, ICC, IHC, F

VAP-SV003 CSP Polyclonal Antibody M, R, B, C, X WB, IP, IHC

SPA-585 ERp57 (Grp58) Polyclonal Antibody H, M, R, B WB

SPA-725 ERp57 (Grp58) Monoclonal Antibody H WB, IP, IHC

SPS-720 ERp72 Polyclonal Antibody H, M, R, B WB

SRA-1400 FKBP59 (Hsp56, p59) Monoclonal Antibody H, B WB, IP, ICC, IHC

SPA-240 GrpE Polyclonal Antibody E. coli WB, IP

SPA-766 Hip Polyclonal Antibody H, M, R, B WB

SRA-1500 HOP (p60) Monoclonal Antibody H, M, R, B, C, X W,B IP

SPA-950 HSF-1 Rat Monoclonal Antibody H, M, R, B WB, IP, ICC

SPA-901 HSF-1 Polyclonal Antibody H, M, R, B, C, D, X WB, IP, ICC

SPA-960 HSF-2 Rat Monoclonal Antibody H, M, R, B WB, IP

SPA-470 Hsp47 (Colligin) Monoclonal Antibody H, M, R, B WB, IHC

SPA-1040 Hsp104 Polyclonal Antibody Y WB, IP

SPA-827 KDEL Antibody (Grp78, Grp94) Antibody H, M, R, B, C, D, X WB, IP, ICC, IHC, F

VAA-PT048 KDEL Receptor Monoclonal Antibody H, M, R, B, C, D, X WB, IP, ICC

VAM-PT046 Membrin Monoclonal Antibody H, R, C WB, IP, ICC

SPA-670 p23 Polyclonal Antibody H, M, R WB

SPA-890 PDI Polyclonal Antibody H, M, R, B, X WB, IP, ICC

SPA-891 PDI Monoclonal Antibody H, M, R, B, C, X WB, ICC, IHC

VAM-SV021 Sec6 Monoclonal Antibody H, M, R, B, C WB, IP, ICC

CTA-123 TCP-1a Rat Monoclonal Antibody M, R, B WB, IP, ICC

CTA-191 TCP-1a Rat Monoclonal Antibody H, M, R, B, D, Y WB, IP, F

CTA-202 TCP-1b Rat Monoclonal Antibody H, M, R, B, C WB

VAP-PT068 UGGT Polyclonal Antibody M, R WB

SPP-767 Hip Recombinant Protein R

SRP-1510 HOP (p60) Recombinant Protein H

SPP-900 HSF-1 Recombinant Protein H

NSP-535 Hsp47 (Colligin) Recombinant Protein H

SPP-650 Active GrpE Recombinant Protein E. coli

SPP-670 p23 Recombinant Protein H

LYC-HL101 HeLa Cell Lysate (Heat Shocked)




Tissue Distribution


Human Diseases

AHSA1 AHA1, activator of Heat Shock 90kDa Protein ATPase homolog 1 (yeast)

AHA1, C14orf3, p38

10598 ATPase activity, Protein folding, Chaperone activity, Protein binding

Broad Cytoplasm, Endoplasmic Reticulum

CABC1 chaperone, ABC1 activity of bc1 complex homolog (S. pombe)

ADCK3, COQ8 56997 Kinase activity, Protein folding, Nucleo-tide binding

Mitochondrion

CALR Calreticulin RO, SSA, cC1qR 811 DNA binding, Calcium homeostasis, Ion binding, Actin organization, Sugar binding, Protein export, Protein binding, Protein folding, Regulation of apoptosis, meiosis and transcription

Broad CytoplasmEndoplasmic reticulumExtracellular environment

CANX Calnexin CNX, IP90, P90 821 Ion binding, Angiogenesis, Sugar binding, Protein folding, Protein secretion

Broad CytoplasmEndoplasmic reticulumMembrane

CDC37 cell division cycle 37 homo-log (S. cerevisiae)

P50CDC37 11140 Protein binding, Protein folding, CDK activity

Cytoplasm

ClpP ClpP caseinolytic peptidase, ATP-dependent, proteolytic subunit homolog (E. coli)

8192 Endopeptidase activity, Proteolysis, Peptidase activity

Broad Mitochondrion

ClpX ClpX caseinolytic peptidase X homolog (E. coli)

10845 Ion binding, Protein folding, Nucleo-tide binding, Protein transport, Protein binding

Broad Mitochondrion

EXOC3 exocyst complex compo-nent 3 [Homo sapiens]

SEC6, SEC6L1, Sec6p

11336 Exocytosis, Protein transport Plasma mem-brane

FKBP1A FK506 binding protein 1A, 12kDa

FKBP1; PKC12; PKCI2; FKBP12; PPIASE; FKBP-12; FKBP12C

2280 Isomerase activity, Protein folding, Protein binding

Broad Cytoplasm, Sarcoplasmic Recticulum

FKBP1B FK506 binding protein 1B, 12.6 kDa

FKBP12.6, FKBP1L, FKBP9, OTK4, PKBP1L, PPIase

2281 Isomerase activity, Muscle contraction, Protein folding

Broadly Cytoplasm Hypertension

FKBP5 FK506 binding protein 5 FKBP51, FKBP54, P54, PPIase, Ptg-10

2289 FK506 binding, Protein folding, Isomerase activity, Protein binding

Broad Nucleus Depression

GOSR2 Golgi SNAP receptor com-plex member 2

Bos1, GS27, Membrin

9570 Receptor activity, Vesicle mediated trans-port, Transporter activity, Protein transport

Golgi apparatus, Endoplasmic reticulum, Mem-brane

HSF1 Heat Shock transcription factor 1

HSTF1 3297 DNA binding, Protein folding, Protein binding, Transcription, Transcriptional Activity



3298 DNA binding, Protein folding, Protein binding, Transcription, Transcriptional Activity



CTM 3299 DNA binding, Cell development, Transcriptional Activity, Cell proliferation, Protein folding, Transcription

Broad Nucleus

HSPA4L Heat Shock 70kDa Protein 4-like

APG-1, Osp94 22824 Nucleotide binding, Protein folding Broad Cytoplasm, Nucleus

HSPBP1 Hsp70-interacting Protein 23640 Broad

KDELR1 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 1 [Homo sapiens]

ERD2, ERD2.1, HDEL, PM23

10945 ER retention, Protein retention, Protein transport

Endoplasmic reticulumGolgi apparatus

KDELR2 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2 [Homo s apiens]

ELP-1; ERD2.2 11014 ER retention, Protein retention, Protein transport

Endoplasmic reticulumGolgi apparatus

KDELR3 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 3 [Homo sapiens]

ERD2L3 11015 ER retention, Protein retention, Protein transport

Endoplasmic reticulumMembrane

PDIA2 Protein disulfide isomerase family A, member 2

PDA2, PDI, PDIP, PDIR

64714 Isomerase activity, Apoptosis, Protein binding, Redox homeostasis, Protein folding, Protein retention

Endoplasmic reticulum


Chaperones & Others (continued)

Grp94 Monoclonal Antibody (Cat. No. SPA-850)Human colon cancer CoCa-2 cells were analyzed by flow cytometry using isotype control antibody (left) or

Grp94 monoclonal antibody (clone 9G10; right) at a final concentration of 10µg/mL.



Tissue Distribution


Human Diseases

PDIA3 Protein disulfide isomer-ase family A, member 3

ERp57, ERp60, ERp61, GRP57, GRP58, P58, PI-PLC

2923 Cysteine endopeptidase activity, Re-dox homeostasis, Phospholipase C ac-tivity, Regulation of apoptosis, Protein binding, Protein import into nucleus, Disulfide isomerase activity, Protein retention in ER, Signal transuction


PDIA3P Protein disulfide isomer-ase family A, member 3 pseudogene

Erp60, GRP58P 171423


Erp70, Erp72 12304 Ion binding, Redox homeostasis, Isomerase activity, Protein secretion, Protein disulfide isomerase activity



FLJ30401, PDIR 10954 Isomerase activity, Electron transport, Oxidoreductase activity, Redox ho-meostasis, Protein folding



ERP5, P5, TXNDC7

10130 Isomerase activity, Redox homeostasis, Protein folding


PTGES3 Prostaglandin E synthase 3 (cytosolic)

P23, TEBP 10728 Isomerase activity, Fatty acid bio-synthesis, Prostaglandin E sytnhase, Prostanoid biosynthesis, Telomerase activity, Signal transduction, Telomere maintenance

Cytoplasm, Nucleus

STIP1 Stress-induced-phospho-protein 1 (Hsp70/Hsp90-organizing protein)

HOP; P60; STI1L 10963 Binding, Response to stress, Protein folding

Golgi, Nucleus

TCP1 t-complex 1 CCT-a, CCT1, CCTa, TCP-1-a

6950 Nucleotide binding, Protein folding Cytoplasm

TOR1A torsin family 1, member A (torsin A)

DQ2, DYT1, torsin A

1861 Endopeptidase activity, Protein folding, Nucleotide binding

Broad Cytoplasmic,, Endoplasmic Reticulum

Dystonia

TOR1B torsin family 1, member B (torsin B)

DQ1 27348 Nucleotide binding, Protein folding Endoplasmic Reticulum

TRAP1 TNF receptor-associated Protein 1

HSP75, HSP90L 10131 Nucleotide binding, Protein folding Broad Mitochondrion

UGCGL1 UDP-glucose ceramide glucosyltransferase-like 1

HUGT1 56886 Glucosyltransferase activity, Protein folding, Amino acid glysoylation


UGCGL2 UDP-glucose ceramide glucosyltransferase-like 2

HUGT2 55757 Glucosyltransferase activity, Protein folding, Amino acid glysoylation


18

TCP-1a Monoclonal Antibody (Cat. No. CTA-191)Human colon cancer Coca-2 cells were analyzed by flow cytometry using isotype control antibody

(left) or TCP-1a monoclonal antibody (clone 91a; right) at a final concentration of 10µg/mL.

Grp75 Monoclonal Antibody (Cat. No. SPS-825)Human breast cancer tissue was immunohistochemically

stained using Grp75 monoclonal antibody (clone 30A5) at a

dilution of 1:50.


Heat shock proteins (HSP), also known as molecular chape-

rones, are critical regulators of cellular homeostasis. Initially

identified some forty years ago as heat responsive genes, HSPs

have been reported to play important roles in the folding of

nascent or new proteins, guiding the renaturation of mis-

folded or partly denatured proteins, as well as facilitating

cellular turnover of client proteins8,12,14. In this regard, HSP90

and its associated co-chaperone complex is known to recruit E3

ubiquitin ligases under certain conditions, favoring the ubiqu-

itinylation and degradation of the client proteins. However, in

the presence of ATP, HSP90 complexes can favor the stabiliza-

tion of these client proteins23.

HSPs are categorized into six different families according to

their respective molecular weights. They are the HSP100 fami-

ly, the HSP90 family, the HSP70 family, the HSP60 family, the

HSP40 family, and the small heat shock family (sHSPs) including

HSP27.

Small Heat Shock FamilyThe small heat shock family (sHSP) of molecular chaperones is

a ubiquitously expressed group of proteins that is highly con-

served among species. To date, ten sHSP isoforms have been

identified and designated HSPB1 through HSPB10, respectively,

with the most common being HSPB1 or HSP27, and HSPB5 or

aB-crystallin14. Both HSP27 and aB-crystallin are constitutively

expressed in a variety of tissues; their expression, however,

is also up-regulated under conditions of stress as well as in a

variety of disease settings14.

Members of the sHSP family are categorized on the basis that

they possess a conserved C-terminal region known as the a-cry-

stallin domain and a variable N-terminal region. The a-crystal-

lin domain consists of two anti-parallel b-sheets14. It is worth

noting that while proteins like HSP32/HO-1 have also been

categorized as sHSPs, they lack the critical C-terminal a-crystal-

lin domain defining this family of heat shock proteins.

The small heat shock family members vary in their respective

molecular weights; they range in size from 15 kDa to 30 kDa.

These proteins are known to exist as either homo- or hetero-

complexes ranging in size from single units to large multimeric

complexes up to approximately 700 kDa3.

It is well documented that sHSP family members undergo

post-translational modifications with the most common being

the phosphorylation of serine residues. For instance, both the

human form of aB-crystallin and HSP27 are phosphorylated on

three serine residues. In the case of aB-crystallin, this protein is

phosphorylated on Ser-19, Ser-45, and Ser-5913; whereas HSP27

is phosphorylated on Ser-15, Ser-78, and Ser-82, respective-

ly16,22.

While little homology exists in the sequences flanking these

phosphorylation sites, there is definite overlap in regard to the

kinases that phosphorylate these sites. In particular, the mito-

gen activated protein kinase activated protein kinase, MAP-

KAPK-2 is one of the key protein kinases able to phosphorylate

many of these sites with the exception of Ser-19 on aB-crystal-

lin, both in vitro and in vivo. At present, the kinase responsible

for phosphorylating Ser-19 of on aB-crystallin has yet to be

identified. Other kinases implicated in the phosphorylation of

these serine sites are Erk-1 and Erk-2, which phosphorylate aB-

crystallin15, and MAPKAPK-3, PKAca, p70S6K, PKD1, and PKCd,

which phosphorylate HSP276,9,16,21,22.

Upstream Signals Leading to the Phosphorylation of HSP27HSP27 has been reported to be phosphorylated in response

to a variety of extracellular-derived signals including TNFa,

thrombin, bFGF stimulation, as well as under conditions of

heat shock and oxidative stress7,16. It is postulated that these

pathways converge on and elicit their effects through p38

MAPK and MAPKAPK-2. p38 MAPK has been reported to phos-

phorylate MAPKAPK-2 in vitro on several residues including

Thr-25, Thr-222, and Thr-334 leading to its activation5. Upon

activation, MAPKAPK-2 is believed to phosphorylate HSP27 in

Hsp27 Review

HSP27: A regulator of cellular invasion. HSP27 localizes to focal

adhesions, influences membrane dynamics and enhances the invasive

phenotype of malignant cells.

20

vivo. MAPKAPK-2, as well as MAPKAPK-3, has been reported

to phosphorylate HSP27 in vitro on all three HSP27 phosphory-

lation sites, Ser-15, Ser-78, and Ser-8216,22. Studies utilizing the

p38 inhibitor, SB203580, have also offered conclusive evidence

that the p38 pathway is intimately involved in the post-trans-

lational regulation of HSP27. Treatment with SB203580, is able

to attenuate the phosphorylation of HSP27 in response to

various agonists18.

More recently, both PKD1 and AKT1 have been ascribed as

HSP27 phosphorylating kinases. PKD1 was shown to phospho-

rylate HSP27 in vitro, however, only on Ser-15 and Ser-829.

AKT1, on the other hand, was shown to interact with p38 and

phosphorylate HSP27 on Ser-8221.

HSP27: FunctionAs a high molecular weight complex, HSP27 plays a critical role

in the renaturation of misfolded or partly denatured proteins

by specifically blocking their aggregation10. As with other

phospho-proteins, this function is tightly linked with the phos-

phorylation status of HSP27. Phosphorylation of Ser-82 has

been shown to result in HSP27 complex dissociation and the

subsequent loss of its chaperoning activity. In addition to its

chaperoning function, HSP27 has been shown to interact with

different cytoskeletal elements affecting actin polymerization4

as well as inhibiting apoptosis7,19,20.

Apoptosis, or programmed cell death, is a finely coordina-

ted process involving the activation of a discrete network of

enzymes, referred to as cellular caspases, that aid in preserving

the fidelity of the human genome as well as turning over

damaged or worn-out cells. While there is variation in terms of

the mechanism by which apoptosis can be elicited (e.g., death

receptor apoptosis vs. mitochondrial mediated apoptosis),

these pathways converge on the key executioners of apoptosis,

caspases-3, –6 and –7, to carry out the process. To counteract

these pro-apoptotic mechanisms, the cell has devised a number

of ways to inhibit this process. Two of the best-defined mecha-

nisms involve the overexpression of the B-cell lymphoma pro-

tein, Bcl-2 and the activation of the anti-apoptotic kinase, AKT.

More recently, HSP27 has also been ascribed as an anti-apopto-

tic protein. In particular, HSP27 has been reported to inhibit

apoptosis (1) through its interactions with the death associated

protein DAXX7, (2) by facilitating the activation of AKT21, and

(3) by blocking the formation of the apoptosome19,20. Taken

together, the overexpression of HSP27 in the context of a

disease such as cancer, would facilitate adaptation to stressful

conditions by aiding in the suppression of apoptosis, ultimately

leading to a more aggressive phenotype. As such, it is not sur-

prising that the overexpression of HSP27 correlates with poor

patient prognosis in a variety of lesions.

HSP27: Clinical RamificationsThere is a wealth of evidence supporting the notion that heat

shock proteins may contribute to the pathogenesis of human

diseases like cancer, cardiovascular disease, and neurological

disorders. Moreover, elevated expression of certain HSPs, like

HSP27, has been reported to correlate with poor patient out-

come in breast, ovarian, and prostate cancer8. This might, in

part, be due to the effects HSP27 has on the cytoskeleton.

Recently, HSP27 has been reported to behave as an actin-cap-

ping protein and influence actin dynamics; the latter of which

was shown to be dependent upon the phosphorylation status

of HSP274,17. In this regard, unphosphorylated monomeric

HSP27 was shown to inhibit the polymerization of actin in

vitro, whereas multimeric HSP27 complexes appeared to have

no inherent effect on actin dynamics regardless of phosphory-

lation status. HSP27 has also been demonstrated to localize to

focal adhesions, influence membrane dynamics, as well as in-

fluence invasive phenotype of cells2,11,24. More recently, HSP27

has been shown to play a role in the regulation of matrix

metalloproteinase (MMP)-2 activity in prostate cancer cells24.

Taken together, it would appear that disrupting the interac-

tions between HSP27 and its binding partners, or reducing its

expression in cancer might be a therapeutically valid approach

when combined with conventional methodologies.

HSP27: Phosphorylation linked to function. HSP27 is phosphorylated

on key serine residues by MAPKAPK2 as well as MAPKAPK3 amongst

others. Phosphorylation is associated with the dimerization of HSP27 and

its function.

References on page 26

21

Initially identified by Ritossa some forty years ago, heat shock

proteins (HSP) were first identified as genes up-regulated in

response to heat shock stimulation in Drosophila20. They are

now recognized as proteins that play critical roles in cellular

homeostasis and the adaptation to stressful conditions such as

heat shock, oxidative stress, genotoxic shock, viral infection,

and hypoxic conditions26. In part, the cytoprotective effects of

HSPs are achieved through their role in the re-folding of partly

denatured or misfolded proteins. HSPs are also known to be

involved in: (1) the folding of newly formed proteins, (2) the

trafficking of cellular proteins, as well as (3) the turn over of

cellular proteins through the proteasomal pathway; as such,

HSPs have been classified as “molecular chaperones”.

HSPs are ubiquitously expressed and highly conserved among

species, ranging from the simplest prokaryotes to complex eu-

karyotes such as humans. They are classified according to their

respective molecular weights and are divided into six families:

the small HSPs (sHSPs), the HSP40 family, the HSP60 family, the

HSP70 family, the HSP90 family, and the HSP100 family.

The HSP70 FamilyThe HSP70 family represents one of the most widely examined

heat shock families and consists of up to ten highly homolo-

gous members. Refer to Table 1 for a representative list of the

HSP70 family members.

As with other heat shock families, members of the HSP70 fami-

ly differ in their spatial and subcellular distribution, as well as

their expression levels under normal, unstressed conditions21,24.

It is well established that the expression of some members of

the HSP70 family can be induced under conditions of stress;

as these proteins do not contain introns, they are able to be

quickly up-regulated.

While the expression of many HSP70 family members can be

up-regulated in response to various stressors, the major stress

inducible HSP70 members are the highly homologous genes

HSP1A1 and HSPA1B, also referred to as HSP70-1 and HSP70-2,

respectively. These proteins are expressed at relatively low or

undetectable levels in most normal, unstressed cells; however,

upon insult, their expression dramatically increases. It is worth

noting, that HSPA6 and HSPA7, the two other highly related

HSP70 inducible members known as HSP70B’ and HSP70B are

up-regulated only under conditions of extreme stress21,24. At

present, further research is required to elucidate the physiolo-

gical importance of these two HSP70 family members.

The constitutively expressed member of HSP70 family is HSPA8,

also referred to as HSC70. HSC70 is ubiquitously expressed in

all cell types and is believed to be responsible for maintaining

normal cellular function. Two other members of the HSP70 fa-

mily under active investigation are the endoplasmic reticulum-

(ER) and mitochondrial-associated members, referred to as the

glucose regulated proteins, GRP78 and GRP75. GRP78 plays

a critical role in the ER-associated stress response, whereas

GRP75 (also known as mortalin) is involved in the maintenance

of mitochondrial function.

HSP70: Structure and FunctionAll HSP70 family members contain a highly conserved N-termi-

nal ATPase domain of approximately 44 kDa which possesses

weak ATPase activity under normal conditions. These proteins

also contain an approximately 25 kDa C-terminal region which

consists of a conserved hydrophobic peptide binding domain

(PBD) of approximately 15 kDa, and a more variable a-helical

domain of approximately 10 kDa5. The a-helical domain is

classified as a “cap” believed to open and close in response to

changes in the nucleotide binding status of HSP7015.

The activity and function of HSP70 are thought to result from

the binding of ATP to the N-terminus. In its ATP-bound state,

the C-terminus of HSP70 is said to undergo a conformational

change, resulting in the opening of the a-helical cap; this

opening allows substrates to interact with the hydrophobic

pocket of the PBD. In its ADP-bound state, it is believed that

the a-helical cap is closed, excluding substrates from the PBD.

Thus, in the presence of ATP, HSP70 is said to favor the folding

of its client protein, as it has a lower affinity and faster proces-

sing rate than the ADP-bound form5,15. However, unlike other

enzyme classes, members of the HSP70 family bind to a wide

variety of client proteins through short hydrophobic segments

found in unfolded, misfolded, or denatured proteins.

On its own, members of the HSP70 family are known to

possess little or no intrinsic ATPase activity. As with other heat

shock proteins, ATPase activity and function are thought to

be influenced through interactions with specific co-chaperone

molecules.

HSP70 co-chaperones include: (1) HSP40, which is believed

to assist in loading targets on the HSP70 machinery3, (2) the

HSC70 interacting protein, Hip, which binds to the ATPase do-

main stimulating its activity3, (3) the HSC70/HSP90 organizing

protein, Hop, which serves as a link between HSP70 and HSP90

allowing for substrate exchange between the two chaperones,

and also facilitates ATP/ADP cycling3, (4) the HSC70 unbin-

ding protein, Hup, which facilitates the release of unfolded

proteins3 , (5) the HSC70 accessory protein, Hap3, and the Bcl-2

associated athanogene proteins, BAG-1, BAG-2, and BAG-3,

which interact with the ATPase domain and block the binding

of unfolded proteins4,11,23,27, and (6) the carboxyl-terminus of

HSP70 interacting protein, CHIP, which is believed to be a bona

Hsp70 Review

22

fide E3 ubiquitin ligase assisting in the ubiquitinylation of

cellular proteins1,10,16.

Overall, members of the HSP70 family are known to play

critical roles in the folding of newly synthesized proteins; the

re-folding of misfolded or denatured proteins; the trafficking

of proteins across cellular membranes; the disassembly of

clathrin-coated vesicles; the inhibition of protein aggregation;

and the targeting and degradation of proteins via the protea-

somal pathway3. More recently, HSP70 has also been demons-

trated to suppress apoptosis in response to various stimuli12.

HSP70: Effects on ApoptosisApoptosis is a highly coordinated process that functions either

through the activation of a discrete network of cysteine pro-

teases known as cellular caspases, or through mechanisms not

depending on caspase activation, known as caspase-indepen-

dent cell death.

The activation of cellular caspases can be achieved through va-

rious mechanisms including death signals provided at the level

of the cell membrane, the mitochondria, and the endoplasmic

reticulum. While these pathways rely on different initiators

of apoptosis, they all converge on, and elicit their effects

through, the executioner caspases — mainly caspase-3, -6 and

-7. Along with the activation of endonucleases, the activation

of these caspases results in the dismantling of the cell and its

intracellular contents, leading to the eventual formation of

apoptotic bodies.

It is well established that the commitment to undergo apopto-

sis can be attenuated or blocked through various mechanisms,

including the activation of key signal transduction molecules

such as Akt, and the overexpression of certain cellular prote-

ins such as Bcl-2. More recently, overexpression of heat shock

proteins — mainly members of the HSP70 family — has also

been demonstrated to inhibit apoptosis. Elevated expression

of HSP70 has been reported to: (1) inhibit the formation of the

apoptosome2, (2) inhibit the translocation of the Bcl-2 protein,

Bax, to the mitochondrial membrane, ultimately blocking the

release of cytochrome c from the mitochondria22, (3) inhibit

the activation of cellular caspases19, (4) block the activation

of the apoptosis signal regulating kinase, ASK118, (5) inhibit

the activation of the stress kinase p388, and (6) inhibit JNK

activation17.

HSP70: Clinical Ramifications in CancerThere is a wealth of literature supporting the notion that heat

shock proteins are elevated in a variety of human malignancies

and that these increases in expression may not only contribute

to the pathogenesis of the disease25, but may be of diagnostic,

prognostic and therapeutic importance6. In this regard, HSP70

has been reported to correlate with poor differentiation in

certain malignancies, increased lymph node metastases, che-

mo-resistance, and poor clinical outcome6,14. Further studies

evaluating the importance of HSP70 family members in the

initiation and progression of cancer will undoubtedly be of

great clinical importance.

HSP70: A cell survival protein. HSP70

suppresses apoptosis by inhibiting the

formation of the apoptosome and by

blocking the activation of stress induced

kinases including: ASK1, p38, and JNK,

respectively.



The heat shock, or stress family of proteins is a highly conser-

ved, ubiquitously expressed class of proteins that have been

demonstrated to be intimately involved in the regulation of

cellular homeostasis in response to a myriad of environmental

and physiological stressors27.

The heat shock proteins (HSP) are classified into six different

groups according to their respective molecular weights; they

are the small heat shock proteins including HSP27, the HSP40

family, the HSP60 family, the HSP70 family, the HSP90 family,

and the HSP100 family, respectively.

HSPs, commonly referred to as molecular chaperones, were

initially identified and described over thirty years ago as heat

shock responsive genes. HSPs are now know to play critical

roles in the stabilization of partly denatured or misfolded pro-

teins, facilitate proper folding of nascent or new polypeptides

as well as regulate the spatial distribution of cellular proteins.

More recently, these molecular chaperones, mainly HSP90,

have received significant attention for the putative roles they

play in the pathogenesis and progression of human diseases

like cancer21,35.

HSP90: Structure and FunctionThe HSP90 family, which consists of both inducible and consti-

tutive isoforms, is encoded at two distinct loci. Cellular ho-

mologues of the HSP90 family include: HSP90a (the inducible

isoform), HSP90b (the constitutive isoform) Grp94 and Trap1,

as well as the recently identified variant HSP90N. Whereas,

HSP90a and HSP90b are predominantly cytosolic proteins and

represent 1-2% of the normal cellular protein content, Grp94

and Trap1 are localized within the endoplasmic reticulum (ER)

and mitochondria, respectively, and are expressed at much

lower levels than their cytoplasmic counterparts28. HSP90N, on

the other hand, preferentially localizes to the cellular membra-

ne through its unique N-terminal hydrophobic region10.

All members of the HSP90 family possess three specific do-

mains: an N-terminal nucleotide binding pocket to which most

clinical compounds are being developed6,22, a central domain

important for ATPase activity11,19, and a C-terminal domain

believed to act as a second nucleotide binding site9. HSP90

can either exist as a homodimer, a heterodimer, or as a multi-

protein complex with other co-chaperones including HSP40,

HSP70, Hop, and p2328. As with other heat shock families, di-

merization is believed to be an ATP-dependent process. Unlike

other member; however, the N-terminal nucleotide binding

site of HSP90 is highly unique and bears a strong resemblance

to members of the GKHL superfamily including bacterial gyra-

se, MutL and histidine kinases8.

The mechanism(s) involved in regulating HSP90 activity and

function, is at present unclear. However thought to involve:

(1) post-translational modification including acetylation and

phosphorylation1,17,20, (2) the N-terminal nucleotide binding

status28, and (3) interactions with accessory co-chaperones28.

Early studies evaluating the phosphorylation status of HSP90

revealed that phosphorylation of this target is essential for its

activity. In this regard, HSP90 has been reported to be tyrosine

phosphorylated in vivo when complexed with other proteins1.

These specific phosphorylation sites have yet to be elucidated,

however. More recently, the acetylation status of HSP90 has

also been reported to influence the activity of HSP90. In par-

ticular, these studies revealed that hyperacetylation of HSP90

led to decrease in its association with the essential co-chapero-

ne, p23, and a concomitant loss of chaperoning activity20. The

specific acetylation sites have been yet to be reported.

The N-terminal nucleotide binding status has also been de-

monstrated to influence the function of HSP90. In the presence

of ATP and the appropriate upstream signals, HSP90 cyclizes

with its co-chaperone molecules, stabilizing the expression

of its client proteins. However, when bound by inhibitors like

Hsp90 Review

left: HSP90: A regulator of cell survival.

Inhibition of HSP90 activity by drugs like

geldanmycin destabilize client proteins which

ultimately leads to the onset of apoptosis.

right: HSP90: A “drugable” target. Inhibi-

tion of HSP90 by geldanmycin (GA) favors

the ubiquitinylation and degradation of client

proteins.

24

Geldanamycin (GA), HSP90 function is impaired which results

in the recruitment of E3 ubiquitin ligases favoring the ubi-

quitinylation and degradation of client proteins by the 26S

proteasomal complex28. The stabilization versus degradation

of proteins, in the presence of physiological stressors, may tip

the balance in favor of stabilizing mutant proteins ultimately

promoting an anti-apoptotic or pro-survival state.

As with other heat shock proteins, HSP90 requires a numb-

er of co-chaperone molecules for its full function including

HSP70, HSP40, Hip/Hop, p23, immunophilins, and CDC37/p5028.

More recently, Aha1 (Activator of HSP90 ATPase homologue

1), which associates with the central domain of HSP90, was

identified as a key molecular co-chaperone required for ATPase

function18.

HSP90: Client ProteinsIn comparison to other members of the heat shock family,

HSP90 client proteins are unique and tend to encompass key

signal transduction molecules involved in the regulation of

cellular growth, survival, and differentiation. In this regard,

one of the first client proteins to be described was the trans-

forming tyrosine kinase isolated from the Rous sarcoma virus,

v-Src30,33. Since this original discovery, the number of client

proteins influenced by HSP90 has significantly increased, many

of which are linked with the pathogenesis of human cancer.

Client proteins include serine/threonine and tyrosine kinases,

transcription factors, and steroid receptors as well as certain

tumor suppressor proteins. A concise list of clients influenced

by HSP90 include: Akt/PKB, ASK1, Aurora B, Bcr-Abl, CDK1,

CDK4, CHK1, CKII, ErbB2/Her-2, EGFR, ER, Hif-1a, c-Met, mu-

tant p53, PLK, and Raf28.

Two key signaling molecules influenced by HSP90, which are

central to normal physiology, are the protein kinase Akt, and

the tumor suppressor protein p53. In the case of Akt, HSP90

has been demonstrated to bind with the phosphorylated form

and protect it from being inactivated by its dephosphorylating

phosphatase, protein phosphatase (PP)-2A25. When active, Akt

is known to provide anti-apoptotic signals, through various

mechanisms, ultimately preventing the cells from undergoing

apoptosis. In this regard, Akt in association with HSP90, has

been demonstrated to phosphorylate and inhibit the apoptotic

kinase ASK1, thus blocking apoptosis36.

In the case of p53, HSP90 has been reported to bind with and

stabilize the expression of the mutated form of this prote-

in29. Stabilization of the mutated form provides a mechanism

of knocking out the function of the normal wild-type p53

molecules through a dominant-negative effect. Functional p53

exists as a tetramer; as such, one mutated copy of p53 within

this complex is capable of impairing normal p53 function. As

p53 has been marked as the master regulator of the human

genome, knocking out this function of this essential prote-

in through stabilization of the mutated form allows for the

propagation of additional favorable oncogenic mutations,

including those that facilitate progression of the disease e.g.,

invasion and metastasis.

HSP90: Clinical Ramifications in CancerSeveral lines of evidence support the notion that the expressi-

on levels of heat shock proteins are dramatically increased in

a variety of human malignancies, both in solid and hematolo-

gical types, and might contribute to the advancement of the

disease3,5,7,12,15,16,21,23,24,26,34,35. As an example, elevated levels

of HSP27 have been reported to correlate with poor patient

outcome in prostate, breast, and ovarian cancer4. Moreover,

compelling evidence suggests that HSP90, in the context of

cancer, exists in a “hyperactive state” in the diseased tissue

when compared with the normal surrounding material14. In

its highly active state, the HSP90 complex would theoretically

influence key signaling nexuses that would contribute to the

pathogenesis of the disease; these include cell growth promo-

tion, evasion of apoptosis, and stimulation of angiogenesis. In

this regard, it has been postulated that changes in expression

and activity levels are critical in that they provide a mechanism

to counteract, or compensate, for the selective pressures these

abnormal cells experience as the disease progresses including

gene mutations, hypoxia, and growth pressures amongst

others. As such, heat shock proteins, mainly HSP90, appear

to provide a buffering mechanism facilitating the “natural

selection” of the strongest cell lineage ultimately allowing for

adaptation to the “harshest” of conditions.

Consequently, based upon the uniqueness of the N-terminal

nucleotide binding site, the differences in biological activity

between the cancer and normal tissue, and the notion that

HSP90 stabilizes key oncogenic client proteins, HSP90 has been

suggested to serve as an excellent target for therapeutic in-

tervention2,13,31. Not only is targeting HSP90 selecting against

those adaptable cell lineages, but in addition, key oncogenic

proteins would be destabilized and consequently degraded,

shifting the balance towards an anti-proliferative pro-apopto-

tic state.

Currently, there are on-going clinical trials evaluating the

efficacy of these N-terminal specific inhibitors and a number

of clinical candidates in the pipeline. Perhaps, the future will

entail a combinatorial modality involving the administration of

selective HSP90 inhibitors with conventional methodologies.


25

Hsp27 References1. Aldrian S, Trautinger F, Frohlich I, Berger W, Micksche M, Kindas-Mugge I. Overexpres-sion of Hsp27 affects the metastatic phenotype of human melanoma cells in vitro. Cell Stress Chaperones. 2002 Apr;7(2):177-185.

2. Aldrian S, Kindas-Mugge I, Trautinger F, Frohlich I, Gsur A, Herbacek I, Berger W, Micksche M. Overexpression of Hsp27 in a human melanoma cell line: regulation of E-cadherin, MUC18/MCAM, and plasminogen activator (PA) system. Cell Stress Chaperones. 2003 Fall;8(3):249-57.

3. Beck FX, Neuhofer W, Muller E. Molecular chaperones in the kidney: distribution, puta-tive roles, and regulation. Am J Physiol Renal Physiol. 2000 Aug;279(2):F203-F215.

4. Benndorf R, Hayess K, Ryazantsev S, Wieske M, Behlke J, Lutsch G. Phosphorylation and supramolecular organization of murine small heat shock protein HSP25 abolish its actin polymerization-inhibiting activity. J Biol Chem. 1994 Aug 12;269(32):20780-20784.

5. Ben-Levy R, Leighton IA, Doza YN, Attwood P, Morrice N, Marshall CJ, Cohen P. Identi-fication of novel phosphorylation sites required for activation of MAPKAP kinase-2. EMBO J. 1995 Dec 1;14(23):5920-5930.

6. Butt E, Immler D, Meyer HE, Kotlyarov A, Laass K, Gaestel M. Heat shock protein 27 is a substrate of cGMP-dependent protein kinase in intact human platelets: phosphory-lation-induced actin polymerization caused by HSP27 mutants. J Biol Chem. 2001 Mar 9;276(10):7108-7113.

7. Charette SJ, Lavoie JN, Lambert H, Landry J. Inhibition of Daxx-mediated apoptosis by heat shock protein 27. Mol Cell Biol. 2000 Oct;20(20):7602-7612.

8. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, pre-dictive, and treatment implications. Cell Stress Chaperones. 2005 Summer;10(2):86 103.

9. Doppler H, Storz P, Li J, Comb MJ, Toker A. A phosphorylation state-specific anti-body recognizes Hsp27, a novel substrate of protein kinase D. J Biol Chem. 2005 Apr 15;280(15):15013-15019.

10. Ehrnsperger M, Graber S, Gaestel M, Buchner J. Binding of non-native protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation. EMBO J. 1997 Jan 15;16(2):221-229.

11. El-Ghobashy AA, Shaaban AM, Innes J, Prime W, Herrington CS. Upregulation of heat shock protein 27 in metaplastic and neoplastic lesions of the endocervix. Int J Gynecol Cancer. 2005 May-Jun;15(3):503-509.

12. Haslbeck M, Franzmann T, Weinfurtner D, Buchner J. Some like it hot: the structure and function of small heat-shock proteins. Nat Struct Mol Biol. 2005 Oct;12(10):842-846.

13. Ito H, Okamoto K, Nakayama H, Isobe T, Kato K. Phosphorylation of aB-crystallin in response to various types of stress. J Biol Chem. 1997 Nov 21;272(47):29934-29941.

14. Kappe G, Franck E, Verschuure P, Boelens WC, Leunissen JA, de Jong WW. The human genome encodes 10 a-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones. 2003 Spring;8(1):53-61.

15. Kato K, Ito H, Kamei K, Inaguma Y, Iwamoto I, Saga S. Phosphorylation of aB-crystal-lin in mitotic cells and identification of enzymatic activities responsible for phosphorylati-on. J Biol Chem. 1998 Oct 23;273(43):28346-28354.

16. Landry J, Lambert H, Zhou M, Lavoie JN, Hickey E, Weber LA, Anderson CW. Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II. J Biol Chem. 1992 Jan 15;267(2):794-803.

17. Miron T, Vancompernolle K, Vandekerckhove J, Wilchek M, Geiger B. A 25-kD inhibi-tor of actin polymerization is a low molecular mass heat shock protein. J Cell Biol. 1991 Jul;114(2):255-261.

18. Muller E, Burger-Kentischer A, Neuhofer W, Fraek ML, Marz J, Thurau K, Beck FX. Possible involvement of heat shock protein 25 in the angiotensin II-induced glomerular mesangial cell contraction via p38 MAP kinase. J Cell Physiol. 1999 Dec;181(3):462-469.

19. Pandey P, Farber R, Nakazawa A, Kumar S, Bharti A, Nalin C, Weichselbaum R, Kufe D, Kharbanda S. Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3. Oncogene. 2000 Apr 13;19(16):1975-1981.

20. Paul C, Manero F, Gonin S, Kretz-Remy C, Virot S, Arrigo AP. Hsp27 as negative regu-lator of cytochrome C release. Mol Cell Biol. 2002 Feb;22(3):816-834.

21. Rane MJ, Pan Y, Singh S, Powell DW, Wu R, Cummins T, Chen Q, McLeish KR, Klein JB. Heat shock protein 27 controls apoptosis by regulating Akt activation. J Biol Chem. 2003 Jul 25;278(30):27828-27835. 22. Stokoe D, Engel K, Campbell DG, Cohen P, Gaestel M. Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian

heat shock proteins. FEBS Lett. 1992 Nov 30;313(3):307-313.

23. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer. 2005 Oct;5(10):761-772.

24. Xu L, Chen S, Bergan RC. MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer. Oncogene. 2006 May 18;25(21):2987-2998.

Hsp70 References1. Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C. Identifica-tion of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol. 1999 Jun;19(6):4535-4545.

2. Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM, Green DR. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol. 2000 Aug;2(8):469-475.

3. Benjamin IJ, McMillan DR. Stress (heat shock) proteins: molecular chaperones in cardio-vascular biology and disease. Circ Res. 1998 Jul 27;83(2):117-132.

4. Bimston D, Song J, Winchester D, Takayama S, Reed JC, Morimoto RI. BAG-1, a nega-tive regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release. EMBO J. 1998 Dec 1;17(23):6871-6878.

5. Bukau B, Horwich AL. The Hsp70 and Hsp60 chaperone machines. Cell. 1998 Feb 6;92(3):351-366.

6. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005 Jun; 10(2): 86-103.

7. Freeman BC, Myers MP, Schumacher R, Morimoto RI. Identification of a regulatory motif in Hsp70 that affects ATPase activity, substrate binding and interaction with HDJ-1. EMBO J. 1995 May 15;14(10):2281-2292.

8. Gabai VL, Meriin AB, Mosser DD, Caron AW, Rits S, Shifrin VI, Sherman MY. Hsp70 prevents activation of stress kinases. A novel pathway of cellular thermotolerance. J Biol Chem. 1997 Jul 18;272(29):18033-18037.

9. Hohfeld J, Minami Y, Hartl FU. Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle. Cell. 1995 Nov 17;83(4):589-98.

10. Kampinga HH, Kanon B, Salomons FA, Kabakov AE, Patterson C. Overexpression of the cochaperone CHIP enhances Hsp70-dependent folding activity in mammalian cells. Mol Cell Biol. 2003 Jul;23(14):4948-4958.

11. Kanelakis KC, Morishima Y, Dittmar KD, Galigniana MD, Takayama S, Reed JC, Pratt WB. Differential effects of the hsp70-binding protein BAG-1 on glucocorticoid receptor folding by the hsp90-based chaperone machinery. J Biol Chem. 1999 Nov 26;274(48):34134-34140.

12. Klein SD, Brune B. Heat-shock protein 70 attenuates nitric oxide-induced apoptosis in RAW macrophages by preventing cytochrome c release. Biochem J. 2002 Mar 15;362(Pt 3):635-641.

13. Li CY, Lee JS, Ko YG, Kim JI, Seo JS. Heat shock protein 70 inhibits apoptosis down-stream of cytochrome c release and upstream of caspase-3 activation. J Biol Chem. 2000 Aug 18;275(33):25665-25671.

14. Luk JM, Lam CT, Siu AF, Lam BY, Ng IO, Hu MY, Che CM, Fan ST. Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values. Proteomics. 2006 Feb;6(3):1049-1057.

15. Moro F, Fernandez-Saiz V, Slutsky O, Azem A, Muga A. Conformational properties of bacterial DnaK and yeast mitochondrial Hsp70. Role of the divergent C-terminal a-helical subdomain. FEBS J. 2005 Jun;272(12):3184-3196.

16. Murata S, Minami Y, Minami M, Chiba T, Tanaka K. CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2001 Dec;2(12):1133-1138.

17. Park HS, Cho SG, Kim CK, Hwang HS, Noh KT, Kim MS, Huh SH, Kim MJ, Ryoo K, Kim EK, Kang WJ, Lee JS, Seo JS, Ko YG, Kim S, Choi EJ. Heat shock protein hsp72 is a negati-ve regulator of apoptosis signal-regulating kinase 1. Mol Cell Biol. 2002 Nov;22(22):7721-7730.

18. Park HS, Lee JS, Huh SH, Seo JS, Choi EJ. Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. EMBO J. 2001 Feb 1;20(3):446-456.

19. Reddy RK, Mao C, Baumeister P, Austin RC, Kaufman RJ, Lee AS. Endoplasmic reti-culum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation. J Biol Chem.

References

26

2003 Jun 6;278(23):20915-20924. 20. Ritossa F. A new puffing pattern induced by temperature shock and DNP in drosophi-la. Experentia. 1962 18(12):571-573.

21. Rohde M, Daugaard M, Jensen MH, Helin K, Nylandsted J, Jaattela M. Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms. Genes Dev. 2005 Mar 1;19(5):570-582.

22. Stankiewicz AR, Lachapelle G, Foo CP, Radicioni SM, Mosser DD. Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. J Biol Chem. 2005 Nov 18;280(46):38729-38739.

23. Takayama S, Bimston DN, Matsuzawa S, Freeman BC, Aime-Sempe C, Xie Z, Morimo-to RI, Reed JC. BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J. 1997 Aug 15;16(16):4887-4896.

24. Tavaria M, Gabriele T, Kola I, Anderson RL. A hitchhiker’s guide to the human Hsp70 family. Cell Stress Chaperones. 1996 Apr;1(1):23-28.

25. Wadhwa R, Takano S, Kaur K, Deocaris CC, Pereira-Smith OM, Reddel RR, Kaul SC. Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis. Int J Cancer. 2006 Jun 15;118(12):2973-2980.

26. Wegele H, Muller L, Buchner J. Hsp70 and Hsp90--a relay team for protein folding. Rev Physiol Biochem Pharmacol. 2004;151:1-44.

27. Zeiner M, Gebauer M, Gehring U. Mammalian protein RAP46: an interaction partner and modulator of 70 kDa heat shock proteins. EMBO J. 1997 Sep 15;16(18):5483-5490.

Hsp90 References1. Adinolfi E, Kim M, Young MT, Di Virgilio F, Surprenant A. Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors. J Biol Chem. 2003 Sep 26;278(39):37344-51.

2. Bagatell R, Whitesell L. Altered Hsp90 function in cancer: a unique therapeutic opportu-nity. Mol Cancer Ther. 2004 Aug;3(8):1021-30.

3. Chant ID, Rose PE, Morris AG. Analysis of heat-shock protein expression in myeloid leukaemia cells by flow cytometry. Br J Haematol. 1995 May;90(1):163-8.

4. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005 Jun; 10(2): 86-103.

5. Ciocca DR, Clark GM, Tandon AK, Fuqua SA, Welch WJ, McGuire WL. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J Natl Cancer Inst. 1993 Apr 7;85(7):570-4.

6. Chadli A, Bouhouche I, Sullivan W, Stensgard B, McMahon N, Catelli MG, Toft DO. Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90. Proc Natl Acad Sci U S A. 2000 Nov 7; 97(23): 12524-12529.

7. Conroy SE, Sasieni PD, Fentiman I, Latchman DS. Autoantibodies to the 90kDa heat shock protein and poor survival in breast cancer patients. Eur J Cancer. 1998 May;34(6):942-3.

8. Dutta R, Inouye M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem Sci. 2000 Jan;25(1):24-8.

9. Garnier C, Lafitte D, Tsvetkov PO, Barbier P, Leclerc-Devin J, Millot JM, Briand C, Maka-rov AA, Catelli MG, Peyrot V. Binding of ATP to heat shock protein 90: evidence for an ATP-binding site in the C-terminal domain. J Biol Chem. 2002 Apr 5;277(14):12208-14.

10. Grammatikakis N, Vultur A, Ramana CV, Siganou A, Schweinfest CW, Watson DK, Raptis L. The role of Hsp90N, a new member of the Hsp90 family, in signal transduction and neoplastic transformation. J Biol Chem. 2002 Mar 8;277(10):8312-20.

11. Huai Q, Wang H, Liu Y, Kim HY, Toft D, Ke H. Structures of the N-terminal and middle domains of E. coli Hsp90 and conformation changes upon ADP binding. Structure. 2005 Apr;13(4):579-90.

12. Jameel A, Skilton RA, Campbell TA, Chander SK, Coombes RC, Luqmani YA. Clinical and biological significance of HSP89 a in human breast cancer. Int J Cancer. 1992 Feb 1;50(3):409-15.

13. Kamal A, Boehm MF, Burrows FJ. Therapeutic and diagnostic implications of Hsp90 activation. Trends Mol Med. 2004 Jun;10(6):283-90.

14. Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC, Burrows FJ. A high-affi-nity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature. 2003 Sep 25;425(6956):407-10.

15. Kaur J, Ralhan R. Differential expression of 70-kDa heat shock-protein in human oral tumorigenesis. Int J Cancer. 1995 Dec 11;63(6):774-9.

16. Kimura E, Enns RE, Alcaraz JE, Arboleda J, Slamon DJ, Howell SB. Correlation of the survival of ovarian cancer patients with mRNA expression of the 60-kD heat-shock protein HSP-60. J Clin Oncol. 1993 May;11(5):891-8.

17. Lees-Miller SP, Anderson CW. Two human 90-kDa heat shock proteins are phosphory-lated in vivo at conserved serines that are phosphorylated in vitro by casein kinase II. J Biol Chem 1989 Feb; 264(5): 2431-7

18. Meyer P, Prodromou C, Liao C, Hu B, Mark Roe S, Vaughan CK, Vlasic I, Panaretou B, Piper PW, Pearl LH. Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery. EMBO J. 2004 Feb 11;23(3):511-9.

19. Meyer P, Prodromou C, Hu B, Vaughan C, Roe SM, Panaretou B, Piper PW, Pearl LH. Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions. Mol Cell. 2003 Mar;11(3):647-58.

20. Murphy PJ, Morishima Y, Kovacs JJ, Yao TP, Pratt WB. Regulation of the dynamics of hsp90 action on the glucocorticoid receptor by acetylation/deacetylation of the chapero-ne. J Biol Chem. 2005 Oct 7;280(40):33792-9.

21. Nanbu K, Konishi I, Mandai M, Kuroda H, Hamid AA, Komatsu T, Mori T. Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Cancer Detect Prev. 1998;22(6):549-55.

22. Prodromou C, Roe SM, O’Brien R, Ladbury JE, Piper PW, Pearl LH. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell. 1997 Jul 11;90(1):65-75.

23. Ralhan R, Kaur J. Differential expression of Mr 70,000 heat shock protein in normal, premalignant, and malignant human uterine cervix. Clin Cancer Res. 1995 Oct;1(10):1217-22.

24. Santarosa M, Favaro D, Quaia M, Galligioni E. Expression of heat shock protein 72 in renal cell carcinoma: possible role and prognostic implications in cancer patients. Eur J Cancer. 1997 May;33(6):873-7.

25. Sato S, Fujita N, Tsuruo T. Modulation of Akt kinase activity by binding to Hsp90. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10832-7.

26. Trieb K, Gerth R, Holzer G, Grohs JG, Berger P, Kotz R. Antibodies to heat shock prote-in 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy. Br J Cancer. 2000 Jan;82(1):85-7.

27. Wegele H, Muller L, Buchner J. Hsp70 and Hsp90--a relay team for protein folding. Rev Physiol Biochem Pharmacol. 2004;151:1-44.

28. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer. 2005 Oct;5(10):761-72.

29. Whitesell L, Sutphin PD, Pulcini EJ, Martinez JD, Cook PH. The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an hsp90-binding agent. Mol Cell Biol. 1998 Mar;18(3):1517-24.

30. Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansa-mycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A. 1994 Aug 30; 91(18): 8324-8328.

31. Workman P. Altered states: selectively drugging the Hsp90 cancer chaperone. Trends Mol Med. 2004 Feb;10(2):47-51.

32. Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L. Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12847-52.

33. Xu Y, Singer MA, Lindquist S. Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):109-14.

34. Yano M, Naito Z, Tanaka S, Asano G. Expression and roles of heat shock proteins in human breast cancer. Jpn J Cancer Res. 1996 Sep;87(9):908-15.

35. Yufu Y, Nishimura J, Nawata H. High constitutive expression of heat shock protein 90 a in human acute leukemia cells. Leuk Res. 1992 Jun-Jul;16(6-7):597-605.

36. Zhang R, Luo D, Miao R, Bai L, Ge Q, Sessa WC, Min W. Hsp90-Akt phosphorylates ASK1 and inhibits ASK1-mediated apoptosis. Oncogene. 2005 Jun 2;24(24):3954-63.


Heat Shock

Molecular Chaperones

Cell Signaling

Cyclic Nucleotides

Steroids & Hormones

Eicosanoids

Cytokines

Kinases

Reactive Oxygen Species

Assay Designs offers a comprehensive portfolio of ELISA kits, antibodies, and proteins.

Our extensive product portfolio contains products covering many research areas, inclu-

ding heat shock and molecular chaperones, cell signaling, cyclic nucleotides, steroids and

hormones, eicosanoids, cytokines, kinases, and reactive oxygen species. The products in-

clude ELISA, EIA, and FPIA kits, monoclonal and polyclonal antibodies, proteins, lumines-

cent reagents, substrates and inhibitors, and many accessory reagents. To meet the needs

of your research, our antibodies are tested in a variety of applications with a number of

species.

Let Assay Designs Simplify Your Science® with products that are extensively tested in-

house and their superior performance documented by hundreds of citations in peer-re-

viewed journals. We are continually expanding our product portfolio to help you meet

your research needs. Please visit our website to view our comprehensive list of products

and research tools.

Hier bestellen Sie in Deutschland!Toll free in Germany: 0800-246 66 51 | [email protected] | www.biomol.de

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BIOMOL GmbH · Waidmannstr. 35 · 22769 Hamburg

Phone: +49 (0)40-853 260 0 · Fax: +49 (0)40-853 260 22

[email protected] · www.biomol.de · www.antibodyworld.com

or toll-free in Germany: Phone: 0800-246 66 51 · Fax: 0800-246 66 52

Technical service: +49 (0)40 - 853 260 27, -23

E-Mail (Technical Service): [email protected]

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BIOMOL GmbHWaidmannstr. 3522769 HamburgGermany

[email protected]

Phone: +49 (0)40-853 260 0Fax: +49 (0)40-853 260 22

TOLL FREE IN GERMANY

Phone: 0800-246 66 51Fax: 0800-246 66 52

Heat Shock Proteins and Molecular Chaperones Price List

CTA-123DCTA-123FCTA-191DCTA-191FCTA-202CCTA-202EEKS-500EKS-600EKS-650EKS-700BEKS-725EKS-750EKS-800EKS-810EKS-895ESP-502DESP-502EESP-540DESP-540EESP-555DESP-555FESP-581DESP-581FESP-715DESP-715FESP-741DESP-741EHPK-101JHPK-102JLYC-HL101FNSP-510BNSP-510FNSP-535BNSP-535FNSP-540BNSP-540ENSP-550BNSP-550ENSP-555BNSP-555EOSA-110COSA-110EOSA-111BCOSA-111BEOSA-111COSA-111EOSA-111FICOSA-111FIEOSA-150EOSA-200COSA-200ESPA-110DSPA-110FSPA-210DSPA-210F

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Anti-TCP-1alpha (CCT), clone 23c (Rat IgG2c)Anti-TCP-1alpha (CCT), clone 23c (Rat IgG2c)Anti-TCP-1alpha (CCT), clone 91a (Rat IgG2a)Anti-TCP-1alpha (CCT), clone 91a (Rat IgG2a)Anti-TCP-1beta, clone PK/8/4/4i/2fAnti-TCP-1beta, clone PK/8/4/4i/2fHsp27 StressXPress ELISA KitHSP60 Antigen StressXPress ELISA KitAnti-Human Hsp60 (total) StressXPress ELISA KitHsp70 StressXPress ELISA kit (B-version)Hsp70B‘ StressXPress ELISA KitAnti-Human Hsp70 (IgG/A/M) StressXPress ELISA KitHeme Oxygenase-1 (HO-1), human, StressXPress ELISA KitHeme Oxygenase-1 (HO-1), Rat StressXPress ELISA KitHsp90alpha StressXpress ELISA KitHsp70-A2 Protein - low EndotoxinHsp70-A2 Protein - low EndotoxinHsp60 Protein - low EndotoxinHsp60 Protein - low EndotoxinHsp70 (Hsp72) Protein - low EndotoxinHsp70 (Hsp72) Protein - low EndotoxinHsp65 Protein - low EndotoxinHsp65 Protein - low EndotoxinHsp27 - low EndotoxinHsp27 - low EndotoxinHsp60 (Mouse) - low EndotoxinHsp60 (Mouse) - low Endotoxin17-AAGGeldanamycinHeLa Cell Lysate, Heat ShockedHsp25 ProteinHsp25 ProteinHsp47 (Colligin) ProteinHsp47 (Colligin) ProteinHsp60 ProteinHsp60 ProteinHO-2 (Heme Oxygenase-2) ProteinHO-2 (Heme Oxygenase-2) ProteinHSP70 (Hsp72) ProteinHSP70 (Hsp72) ProteinAnti-HO-1, clone HO-1-1Anti-HO-1, clone HO-1-1Anti-HO-1 (Heme Oxygenase, Hsp32), clone HO-1-2, Biotin ConjugateAnti-HO-1 (Heme Oxygenase, Hsp32), clone HO-1-2, Biotin ConjugateAnti-HO-1 (Heme Oxygenase, Hsp32), clone HO-1-2Anti-HO-1 (Heme Oxygenase, Hsp32), clone HO-1-2Anti-HO-1 (Heme Oxygenase, Hsp32), clone HO-1-2, FITC conjugatedAnti-HO-1 (Heme Oxygenase, Hsp32), clone HO-1-2, FITC conjugatedAnti-HO-1 (Heme Oxygenase-1, Hsp32)Anti-HO-2 (Heme Oxygenase-2)Anti-HO-2 (Heme Oxygenase-2)Anti-Cpn10Anti-Cpn10Anti-GroESAnti-GroES

Cat. No. Product Size Price E


SPA-221DSPA-221FSPA-222DSPA-222FSPA-223DSPA-223FSPA-224DSPA-224FSPA-225CSPA-225ESPA-226CSPA-226ESPA-227CSPA-227ESPA-230DSPA-230FSPA-240DSPA-240FSPA-400CSPA-400ESPA-410DSPA-410FSPA-450ESPA-470DSPA-470FSPA-523DSPA-523FSPA-523PUCSPA-523PUESPA-524DSPA-524FSPA-524PUCSPA-524PUESPA-525CSPA-525ESPA-585CSPA-585ESPA-600DSPA-600FSPA-601DSPA-601FSPA-670CSPA-670ESPA-725CSPA-725ESPA-754ESPA-756DSPA-757CSPA-757ESPA-766CSPA-766ESPA-796ESPA-800BDSPA-800BFSPA-800FIDSPA-800FIFSPA-801ESPA-803DSPA-803FSPA-806DSPA-806FSPA-807DSPA-807FSPA-810APDSPA-810APFSPA-810BDSPA-810BFSPA-810D

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Anti-alpha A CrystallinAnti-alpha A CrystallinAnti-alpha B Crystallin, clone 1B6.1-3G4Anti-alpha B Crystallin, clone 1B6.1-3G4Anti-alpha B CrystallinAnti-alpha B CrystallinAnti-alpha A/alpha B-CrystallinAnti-alpha A/alpha B-CrystallinAnti-phospho-Crystallin, alphaB (Ser19)Anti-phospho-Crystallin, alphaB (Ser19)Anti-phospho-Crystallin, alphaB (Ser45)Anti-phospho-Crystallin, alphaB (Ser45)Anti-phospho-Crystallin, alphaB (Ser59)Anti-phospho-Crystallin, alphaB (Ser59)Anti-beta-Crystallin, clone 3.H9.2Anti-beta-Crystallin, clone 3.H9.2Anti-GrpEAnti-GrpEAnti-Hsp40 (Heat Shock Protein 40, HDJ1)Anti-Hsp40 (Heat Shock Protein 40, HDJ1)Anti-DnaJAnti-DnaJAnti-Hsp40 (Heat Shock Protein 40, HDJ1), clone 2E1Anti-Hsp47 (Colligin), clone M16.10A1Anti-Hsp47 (Colligin), clone M16.10A1Anti-phospho-Hsp27 (Ser78) (Heat Shock Protein 27)Anti-phospho-Hsp27 (Ser78) (Heat Shock Protein 27)Anti-phospho-Hsp27 (Ser78) (Heat Shock Protein 27)Anti-phospho-Hsp27 (Ser78) (Heat Shock Protein 27)Anti-phospho-Hsp27 (Ser82)Anti-phospho-Hsp27 (Ser82)Anti-phospho-Hsp27 (Ser82) (Heat Shock Protein 27)Anti-phospho-Hsp27 (Ser82) (Heat Shock Protein 27)Anti-phospho-Hsp27 (Ser15) (Heat Shock Protein 27)Anti-phospho-Hsp27 (Ser15) (Heat Shock Protein 27)Anti-ERp57 (Grp58)Anti-ERp57 (Grp58)Anti-CalreticulinAnti-CalreticulinAnti-Calreticulin, clone FMC75Anti-Calreticulin, clone FMC75Anti-p23Anti-p23Anti-Erp57, clone MaP.Erp57Anti-Erp57, clone MaP.Erp57Anti-Hsp70B (Heat Shock Protein 70B), clone 165fAnti-Hsp70B (Heat Shock Protein 70B)Anti-Hsp70, Hsc70 (Heat Shock Protein 70, Heat Shock Cognate Protein 70)Anti-Hsp70, Hsc70 (Heat Shock Protein 70, Heat Shock Cognate Protein 70)Anti-HipAnti-HipAnti-Hsp20 (Heat Shock Protein 20)Anti-Hsp27 (Heat Shock Protein 27), Biotin conjugate, clone G3.1Anti-Hsp27 (Heat Shock Protein 27), Biotin conjugate, clone G3.1Anti-Hsp27 (Heat Shock Protein 27), clone G3.1, FITC conjugatedAnti-Hsp27 (Heat Shock Protein 27), clone G3.1, FITC conjugatedAnti-Hsp25 (Heat Shock Protein 25)Anti-Hsp27 (Heat Shock Protein 27)Anti-Hsp27 (Heat Shock Protein 27)Anti-Hsp60 (Heat Shock Protein 65), clone LK-1Anti-Hsp60 (Heat Shock Protein 65), clone LK-1Anti-Hsp60 (Heat Shock Protein 65), clone LK-2Anti-Hsp60 (Heat Shock Protein 65), clone LK-2Anti-Hsp70 (Heat Shock Protein, Hsp72), clone C92F3A-5, AP-conjugatedAnti-Hsp70 (Heat Shock Protein, Hsp72), clone C92F3A-5, AP-conjugatedAnti-Hsp70 (Heat Shock Protein, Hsp72), clone C92F3A-5, Biotin-conjugatedAnti-Hsp70 (Heat Shock Protein, Hsp72), clone C92F3A-5, Biotin-conjugatedAnti-Hsp70 (Heat Shock Protein, Hsp72), clone C92F3A-5


SPA-810FSPA-810FIESPA-810FIHSPA-811DSPA-811FSPA-812CSPA-812ESPA-815APDSPA-815APFSPA-815DSPA-815FSPA-816DSPA-816FSPA-820APDSPA-820APFSPA-820DSPA-820FSPA-822DSPA-822FSPA-826DSPA-826FSPA-827DSPA-827FSPA-828CSPA-828ESPA-829CSPA-829ESPA-830DSPA-830FSPA-835DSPA-835FSPA-840DSPA-840FSPA-842CSPA-842ESPA-843CSPA-843ESPA-845DSPA-845FSPA-846CSPA-846ESPA-860DSPA-860FSPA-865DSPA-865FSPA-890DSPA-890FSPA-891DSPA-891FSPA-895DSPA-895FSPA-896CSPA-896ESPA-897ESPA-901DSPA-901FSPA-950CSPA-950ESPA-960CSPA-960ESPA-1040DSPA-1040FSPA-1101DSPA-1101FSPA-1103DSPA-1103FSPP-225JSPP-225L

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450228470211421211421212493207479212378212493207450207450207450207421144293

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Anti-Hsp70 (Heat Shock Protein, Hsp72), clone C92F3A-5Anti-Hsp70 (Heat Shock Protein 70), clone C92F3A-5, FITC conjugatedAnti-Hsp70 (Heat Shock Protein 70), clone C92F3A-5, FITC conjugatedAnti-Hsp70 (Heat Shock Protein, Hsp72)Anti-Hsp70 (Heat Shock Protein, Hsp72)Anti-Hsp70 (Heat Shock Protein, Hsp72)Anti-Hsp70 (Heat Shock Protein, Hsp72)Anti-Hsc70 (Hsp73), clone 1B5 (Rat), AP-conjugatedAnti-Hsc70 (Hsp73), clone 1B5 (Rat), AP-conjugatedAnti-Hsc70 (Hsp73), clone 1B5 (Rat)Anti-Hsc70 (Hsp73), clone 1B5 (Rat)Anti-Hsc70 (Hsp73)Anti-Hsc70 (Hsp73)Anti-Hsp70/Hsc70, AP conjugateAnti-Hsp70/Hsc70, AP conjugateAnti-Hsp70/Hsc70 (Heat Shock Pro. 70, HS Cognate Pro. 70), clone N27F3-4Anti-Hsp70/Hsc70 (Heat Shock Pro. 70, HS Cognate Pro. 70), clone N27F3-4Anti-Hsp70, Hsc70 (Heat Shock Pro. 70, HS Cognate Pro. 70), clone BB70Anti-Hsp70, Hsc70 (Heat Shock Pro. 70, HS Cognate Pro. 70), clone BB70Anti-Grp78 (BiP)Anti-Grp78 (BiP)Anti-KDEL, clone 10C3Anti-KDEL, clone 10C3Anti-Hsp60 (Heat Shock Protein 60)Anti-Hsp60 (Heat Shock Protein 60)Anti-Hsp60 (Heat Shock Protein 65), clone Mab-11-13Anti-Hsp60 (Heat Shock Protein 65), clone Mab-11-13Anti-Hsp90 (Heat Shock Protein 90), clone AC88Anti-Hsp90 (Heat Shock Protein 90), clone AC88Anti-Hsp90 (Heat Shock Protein 90), clone 16F1Anti-Hsp90 (Heat Shock Protein 90), clone 16F1Anti-Hsp90 alpha, clone 9D2Anti-Hsp90 alpha, clone 9D2Anti-Hsp90 beta (Heat Shock Protein 90b), clone K3705Anti-Hsp90 beta (Heat Shock Protein 90b), clone K3705Anti-Hsp90 beta (Heat Shock Protein 90b), clone K3701Anti-Hsp90 beta (Heat Shock Protein 90b), clone K3701Anti-Hsp90 (Heat Shock Protein 90), clone 2D12Anti-Hsp90 (Heat Shock Protein 90), clone 2D12Anti-Hsp90 (Heat Shock Protein 90)Anti-Hsp90 (Heat Shock Protein 90)Anti-Calnexin-CAnti-Calnexin-CAnti-CalnexinAnti-CalnexinAnti-PDI (Protein Disulfide Isomerase)Anti-PDI (Protein Disulfide Isomerase)Anti-PDI (Protein Disulfide Isomerase), clone 1D3Anti-PDI (Protein Disulfide Isomerase), clone 1D3Anti-HO-1 (Hsp32, Heme Oxygenase-1)Anti-HO-1 (Hsp32, Heme Oxygenase-1)Anti-HO-1 (Hsp32, Heme Oxygenase-1)Anti-HO-1 (Hsp32, Heme Oxygenase-1)Anti-HO-2 (Heme Oxygenase-2)Anti-HSF-1Anti-HSF-1Anti-HSF-1, clone 10H8 (Rat)Anti-HSF-1, clone 10H8 (Rat)Anti-HSF-2, Rat monoclonal IgG 3F2Anti-HSF-2, Rat monoclonal IgG 3F2Anti-Hsp104 (Heat Shock Protein 104)Anti-Hsp104 (Heat Shock Protein 104)Anti-Hsp110/70 (Family)Anti-Hsp110/70 (Family)Anti-Hsp104 (Heat Shock Protein 104)Anti-Hsp104 (Heat Shock Protein 104)Crystallin, alphaCrystallin, alpha


BIOMOL GmbH Bestellen in DeutschlandFon: 0800-2 46 66 51 · Fax: 0800-2 46 66 52

[email protected] · www.biomol.deTechnischer Support: [email protected]

discontinued


SPP-226BSPP-226FSPP-227BSPP-227FSPP-400BSPP-400ESPP-610CSPP-610GSPP-620CSPP-620ESPP-620FSPP-640DSPP-640FSPP-650CSPP-650ESPP-650FSPP-715FSPP-730DSPP-730FSPP-732BSPP-732ESPP-741BSPP-741DSPP-741FSPP-742BSPP-742ESPP-751DSPP-751FSPP-752BSPP-752ESPP-758BSPP-758ESPP-762BSPP-762ESPP-765BSPP-765ESPP-767ESPP-770BSPP-770ESPP-776DSPP-776FSPP-900BSPP-900ESPS-771DSPS-771FSPS-825DSPS-870DSPS-870FSPS-875DSPS-875FSRA-1400DSRA-1400FSRA-1500DSRA-1500FSRP-1510BSRP-1510EVAA-PT048CVAA-PT048EVAM-PT046CVAM-PT046EVAM-SV021CVAM-SV021EVAP-PT068CVAP-PT068EVAP-SV003D

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Crystallin, alphaACrystallin, alphaACrystallin, alphaBCrystallin, alphaBHsp40 ProteinHsp40 ProteinGroEL ProteinGroEL ProteinGroES ProteinGroES ProteinGroES ProteinDnaJ ProteinDnaJ ProteinGrpE ProteinGrpE ProteinGrpE ProteinHsp27 ProteinHO-1 (Hsp32, Heme Oxygenase-1)HO-1 (Hsp32, Heme Oxygenase-1)HO-1 (Hsp32, Heme Oxygenase-1) ProteinHO-1 (Hsp32, Heme Oxygenase-1) ProteinHsp60 ProteinHsp60 ProteinHsp60 ProteinHsp60 ProteinHsp60 ProteinHsc70 (Hsp73) Active ProteinHsc70 (Hsp73) Active ProteinHsc70 (Hsp73) Protein-ATPase FragmentHsc70 (Hsp73) Protein-ATPase FragmentHsp70 Protein, ratHsp70 Protein, ratHsp70B‘ ProteinHsp70B‘ ProteinGrp78 (BiP) ProteinGrp78 (BiP) ProteinHip ProteinHsp90 ProteinHsp90 ProteinHsp90 alpha ProteinHsp90 alpha ProteinHSF-1 ProteinHSF-1 ProteinAnti-Hsp90 alphaAnti-Hsp90 alphaAnti-Grp75, clone 30A5Anti-GroEL, clone 9A1/2Anti-GroEL, clone 9A1/2Anti-GroELAnti-GroELAnti-FKBP59 (Hsp56, p59), clone KN382/EC1Anti-FKBP59 (Hsp56, p59), clone KN382/EC1Anti-Hop (p60), clone DS14F5Anti-Hop (p60), clone DS14F5HOP (p60) ProteinHOP (p60) ProteinAnti-KDEL Receptor, clone KR-10Anti-KDEL Receptor, clone KR-10Anti-Membrin, clone 4HAD6Anti-Membrin, clone 4HAD6Anti-rSec6, clone 9H5Anti-rSec6, clone 9H5Anti-UGGTAnti-UGGTAnti-Cysteine String Protein (CSP)


Alle Preise zzgl. MwSt. und Versandkosten.Preisänderungen und Irrtümer vorbehalten. 06/2007

Your antibody reference: www.antibodyworld.com

CONTACT US TODAY

BIOMOL GmbHWaidmannstr. 3522769 HamburgGermany

[email protected]

Phone: +49 (0)40-853 260 0Fax: +49 (0)40-853 260 22

TOLL FREE IN GERMANY

Phone: 0800-246 66 51Fax: 0800-246 66 52