Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.
-
Upload
clare-grant -
Category
Documents
-
view
260 -
download
2
Transcript of Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.
![Page 1: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/1.jpg)
Molecular Biology ofTHE CELL4th edition
Chapter 15Cell Communication
![Page 2: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/2.jpg)
Cell Communication
Single cell
Multicellular organism
![Page 3: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/3.jpg)
GENERAL PRINCIPLES OF CELL COMMUNICATION
Extracellular signal molecules bind to specific receptors
![Page 4: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/4.jpg)
Extracellular signal molecules can act over either short or long distance
![Page 5: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/5.jpg)
Autocrine signaling can coordinate decision by groups of identical cells
“Community effect” in early developmentIn tumor biology---cancer cells stimulate their own proliferation
![Page 6: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/6.jpg)
Gap junctions allow signaling information to be shared by neighboring cells
Ca2+, cAMP etc. but not for proteins or nucleic acids
Intracellular electrodes, small water-soluble dyes
Connexin 43 deficiency --- abnormal heart development
![Page 7: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/7.jpg)
Each cell is programmed to respond to specific combinations of extracellular signal molecules
![Page 8: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/8.jpg)
Different cells can respond differently to the same extracellular signal molecules
![Page 9: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/9.jpg)
The concentration of a molecule can be adjusted quickly only if the lifetime of the molecule is short
![Page 10: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/10.jpg)
Nitric oxide gas signals by binding directly to an enzyme inside the target cell
Nitroglycerine --- anginaViagra --- PDE inhibitorCO
![Page 11: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/11.jpg)
Nuclear receptors are ligand-activated gene regulatory proteins
![Page 12: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/12.jpg)
Ligand-binding domain
![Page 13: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/13.jpg)
![Page 14: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/14.jpg)
The three largest classes of cell-surface receptor proteins are ion-channel-linked, G-proteins-linked, and enzyme-linked receptors
![Page 15: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/15.jpg)
Most activated cell-surface receptors relay signals via small molecules and a network of intracellular signaling proteins
SCIENCE 281, 1671-1674 (1998)A Mammalian Scaffold Complex That Selectively Mediates MAP Kinase Activation(JNK interacting protein-1. JIP-1)Alan J. Whitmarsh, Julie Cavanagh, Cathy Tournier, Jun Yasuda, Roger J. Davis*
![Page 16: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/16.jpg)
Some intracellular signaling proteins act as molecular switches
~2% of human genes(576 kinases in human genome)
Monomeric GTPaseTrimeric GTPase
![Page 17: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/17.jpg)
Signal integration by protein phosphorylation
![Page 18: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/18.jpg)
Intracellular signaling complexes enhance the speed, efficiency, and specificity of the response
![Page 19: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/19.jpg)
Complex forms transiently
![Page 20: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/20.jpg)
Interactions between intracellular signaling proteins are mediated by modular binding domains
![Page 21: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/21.jpg)
SCIENCE 278, 2075-2080 (1997)Signaling Through Scaffold, Anchoring, and Adaptor ProteinsTony Pawson and John D. Scott
![Page 22: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/22.jpg)
PDZ DomainDomain binding and function: PDZ domains bind to the C-terminal 4–5 residues of their target proteins, frequently transmembrane receptors or ion channels. These interactions can be of high affinity (nM Kd). The consensus binding sequence contains a hydrophobic residue, commonly Val or Ile, at the very C-terminus. Residues at the –2 and –3 positions are important in determining specificity. PDZ domains can also heterodimerize with PDZ domains of different proteins, potentially regulating intracellular signaling. In addition to engaging in protein-protein interactions, several PDZ domains including those of syntenin, CASK, Tiam1 and FAP are capable of binding to the phosphoinositide PIP2. PIP2-PDZ domain binding is thought to control the association of PDZ domain-containing proteins with the plasma membrane.Structure Reference: Doyle, D.A. et al. (1996) Cell 85(7), 1067–1076.
The third PDZ domain from PSD-95.
www.cellsignal.com
![Page 23: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/23.jpg)
Cells can respond abruptly to a gradually increasing concentration of an extracellular signal
Chicken oviduct cells Stimulated by estradiol
effector/target : 1~16
maximal activation
![Page 24: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/24.jpg)
One type of signaling mechanism expected to show a steep threshold-like response
![Page 25: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/25.jpg)
A cell can remember the effect of some signals
Signals trigger muscle cell determination
![Page 26: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/26.jpg)
Cells can adjust their sensitivity to a signal
![Page 27: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/27.jpg)
SIGNALING THROUGH G-PROTEIN-LINKEDCELL-SURFACE RECEPTORS
1. The largest family of cell-surface receptors2. 5% of the C. elegans genes3. Signal molecules: hormones, neurotransmitters and local medicators4. Rhodopsin-light receptor5. Genome sequencing --- vast numbers of new family members6. Major targets for drug discovery
![Page 28: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/28.jpg)
Trimeric G proteins disassemble to relay signals from G-protein-linked receptors
Transducin-G protein in visual transduction
![Page 29: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/29.jpg)
The disassembly of a activated G-protein into two signaling components
![Page 30: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/30.jpg)
The switching off of the G-protein subunit by the hydrolysis of its bound GTP
RGS proteins --- regulators of G protein signaling, act as subunit-specific GTPase activating proteins (GAPs)
~25 RGS proteins in the human genome
![Page 31: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/31.jpg)
Some G-proteins signal by regulating the production of cyclic AMP
Nerve cell culture, preloaded with a fluorescent protein that changes its fluorescence when it binds to cAMP.
>10-6 M~5 X 10-8 M
(Science 260:222-226, 1993)
![Page 32: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/32.jpg)
cAMP-dependent protein kinase (PKA) mediate most of the effects of cyclic AMP
Role of cAMP, PKA in glycogenmetabolism
![Page 33: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/33.jpg)
How gene transcription is activated by a rise in cAMP concentration
(CRE, cAMP response element)
Role of protein phosphatases?
![Page 34: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/34.jpg)
Some G-proteins activate the inositol phospholipid signaling pathway by activating phospholipase C-
(<1% of total phospholipids)
![Page 35: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/35.jpg)
![Page 36: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/36.jpg)
The two branches of the inositol phospholipid pathway
![Page 37: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/37.jpg)
Ca2+ functions as a ubiquitous intracellular messenger
Ca2+ signaling in fertilization of starfish, detected by Ca2+-sensitive fluorescence dye
![Page 38: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/38.jpg)
The main ways eucaryotic cells maintain a very low concentration of free Ca2+ in their cytosol
![Page 39: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/39.jpg)
The frequency of Ca2+ oscillations influences a cell’s response
In a liver cell
![Page 40: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/40.jpg)
Ca2+/calmodulin-dependent protein kinases (CaM-kinases) mediate many of the actions of Ca2+ in animal cells
The structure of Ca2+/calmodulin
A peptide derived from CaM-Kinase II
![Page 41: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/41.jpg)
The activation of CaM-kinases II
~2% of total mass in some brain regions, especially in synapses
It can function as a molecular memory device ---(1) Learning defect (where things are in space) in mutant mice that lack the brain-specific subunit of CaM-kinase II(2) Same defect also observed in mutant mice that have their CaM-kinase II mutated at the autophosphorylation site
![Page 42: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/42.jpg)
CaM-kinases II as a frequency decoder of Ca2+ oscillations
CaM-kinase II is immobilized on a solid surface +a brain protein phosphatase +repetitive pulse of Ca2+/calmodulin at different frequencyKinase activity assay
[Science. 1998 Jan 9;279(5348):227-30.]
![Page 43: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/43.jpg)
Smell and vision depend on G-protein-linked receptors that regulate cyclic-nucleotide-gated ion channels
![Page 44: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/44.jpg)
Cyclic GMPA rod photoreceptor cell
![Page 45: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/45.jpg)
The response of a rod photoreceptor cell to light
![Page 46: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/46.jpg)
Extracellular signals are greatly amplified by the use of small intracellular mediators and enzymatic cascades
Amplification in the light-induced
catalytic cascade in vertebrate rods
![Page 47: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/47.jpg)
G-protein-linked receptors desensitization depends on receptor phosphorylation
![Page 48: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/48.jpg)
SIGNALING THROUGH ENZYME-LINKEDCELL-SURFACE RECEPTORS
Six classes:
1. Receptor tyrosine kinases2. Tyrosine kinase-associated receptors3. Receptorlike tyrosine phosphatases4. Receptor serine/threonine kinases5. Receptor guanylyl cyclases6. Histidine-kinase-associated receptors
![Page 49: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/49.jpg)
Activated tyrosine kinases phosphorylate themselves
angiogenesiscell/axon migration
![Page 50: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/50.jpg)
Three ways in which signaling proteins can cross-link receptor chains
Monomeric vs. dimeric ligand
![Page 51: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/51.jpg)
Inhibition of signaling through normal receptor tyrosine kinases by an excess of mutant receptors
As a tool for determining normal function of receptor
![Page 52: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/52.jpg)
Phosphorylated tyrosine serves as docking sites for proteins with SH2 domains
![Page 53: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/53.jpg)
The binding of SH2-containing intracellular signaling proteins to an activated PDGF receptor
determine the binding specificity
![Page 54: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/54.jpg)
Ras is activated by a guanine nucleotide exchange factor
GEF: guanine nucleotide exchange factorGAP: GTPase-activating protein
In cells [GTP] > [GDP] ~10 fold
![Page 55: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/55.jpg)
The activation of Ras by an activated receptor tyrosine kinase
![Page 56: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/56.jpg)
The MAP-kinase serine/threonine phosphorylation pathway activated by Ras
![Page 57: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/57.jpg)
The organization of MAP-kinase pathway by scaffold proteins in budding yeast
![Page 58: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/58.jpg)
PI 3-kinase produces inositol phospholipid docking sites in the plasma membrane
Cell division vs. cell growthPI 3 kinase is one of the major cell growth signaling transduces
![Page 59: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/59.jpg)
The recruitment of signaling proteins with PH domains to the plasma membrane during B cell activation
SH2domain
Mutation of BTKleads to severely deficiency in Abproduction
![Page 60: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/60.jpg)
The PI 3-kinase/protein kinase B signaling pathway can stimulate cells to survive and grow
![Page 61: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/61.jpg)
Brief summarization
![Page 62: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/62.jpg)
Signal proteins of the TGF- superfamily act through receptor serine/threonine kinases and Smads
![Page 63: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/63.jpg)
Kinase catalytic domain ~250 amino acids
![Page 64: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/64.jpg)
SIGNALING PATHWAY THAT DEPENDS ON REGULATED PROTEOLYSIS
1. Notch2. Wnt3. Hedgehog4. NF-kB
![Page 65: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/65.jpg)
The receptor protein Notch is activated by cleavage
In Drosophila, mutation in Delta leads to produce a huge excess of neurons at the expense of epidermal cells
![Page 66: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/66.jpg)
The processing and activation of Notch by proteolytic cleavage
Inhibit neural differentiation
![Page 67: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/67.jpg)
Wnt proteins bind to Frizzled receptors and inhibit the degradation of -catenin
(c-Myc protein)(APC, adenomatous polyposis coli,a tumor suppressor )
![Page 68: Molecular Biology of THE CELL 4 th edition Chapter 15 Cell Communication.](https://reader030.fdocuments.in/reader030/viewer/2022033014/56649d0c5503460f949e03c7/html5/thumbnails/68.jpg)
Multiple stressful and proinflammatory stimuli act through an NF-B-dependent signaling pathway
inflammationdevelopmentcancer