Evolution of the Protein Kinase Family Michael Gribskov DEPARTMENT OF BIOLOGICAL SCIENCES.
Transcript of Evolution of the Protein Kinase Family Michael Gribskov DEPARTMENT OF BIOLOGICAL SCIENCES.
Evolution of the Protein Kinase Family
Michael Gribskov
DEPARTMENT OF BIOLOGICAL SCIENCES
Protein - PProtein
ProteinKinase
Protein Phosphatase
Are Kinases PhosphoComputers?
• multiple sites = AND or OR calculators
P
P
P
PAND
OR
PX
PX
Kinase Roles
• Protein kinases play essential roles in eukaryotic cells
• Regulation of cell cycle, including structural elements• Regulation of enzymes• "signal transducer"
• response to environment• response to injury/disease/infection
• signal receiver
SignalingCascades
Protein Kinases
• Ser-Thr-Tyr Kinases are common to Eukaryotes (ePK)• Two component Systems (Histidine Kinases)
• Bacteria (HK >epK)• Archaea (HK >ePK)
• Fungi (ePK > HK)• Animals (ePK > HK)• Plants (ePK > HK)
Archael ePKs
Kennelly, P.J., (2003) Biochem. J. 379-389
Bacterial ePKs
• ePK?
• Pkn family• ABC1 family• RIO
Core Protein Kinases
• Ubiquitous• No extra domains• Paradigms: CK1, MAPK
• cell cycle• meiosis/mitosis• circadian cycle
MAPK Cascades in Yeast
Complex Kinases
• AGC family• CAMK family
• Second messenger regulated• Interact with regulatory subunits• Frequently become fused
Protein Kinase Superfamily
PKA
PKCPKGPKBcdk2
srcEGFR
Kinase Core
Catalytic SubunitRegulatory Subunit
DD cAMP cAMP
SH3 SH2
PH
C1 C2
EGF Binding Domain
DD cGMP cGMP
Kinase Roles
• Protein kinases play essential roles in eukaryotic cells
• Regulation of cell cycle, including structural elements• Regulation of enzymes• "signal transducer"
• response to environment• response to injury/disease/infection
• signal receiver
Some Receptor Kinases
(EGF receptor) (Insulin receptor) (FGF receptor)
Receptor Kinases
• Tyr-kinase in animals• Ser-Thr in plants• His in fungi and bacteria
• Clearly the last role to evolve
Receptor Tyrosine Kinase Activation
Complete Kinase Clustering
Yeast Signaling (MAPK)
Validating Transgenomic Predictions
SnRK
• At AKIN10 and AKin11• Rescue yeast SNF1 deletion• Functional homolog
GIN4/ERC47/CLA6/D9719.13/YDR507C KCC4/YCL024W HSL1/(SEL2)/NIK1/YKL453/YKL101W SNF1/CAT1/GLC2/CCR1/PAS14/HAF3/D8035.20/YDR477W
At5g39440 At3g29160/AKIN11 At3g01090/AKIN10 At5g58380 At5g07070 At5g01810 At5g45820 At4g30960 At5g25110 At5g10930 At2g25090 At2g30360 At5g01820/AtSR1 At2g38490 At3g23000/AtSR2 At4g14580 At1g01140 At1g30270 At2g26980 At4g24400 At5g35410/SOS2 At1g48260 At3g17510 At5g57630 At1g60940 At1g10940 At5g08590 At5g63650 At2g23030 At1g78290 At3g50500 At5g66880 At4g33950 At4g40010 At1g29230 At2g34180 At4g18700 At5g45810
KIN1/YD9727.17/YDR122W KIN2/L8004.3/L2546/YLR096W KIN4/KIN31/(KIN3)/O5220/YOR233W YPL141C/LPI5 YPL150W/P2597
50
E=10-80
See
Fig
. 2
Kinase Clustering and Classification
• Arabidopsis & Rice• Human• Drosophila• C. elegans• Yeast
CDC2
?
CDK7
PITSLRE
CRK7
PlantSpecific
Protein Kinase Family Size
• Yeast 130• C. elegans 454• D. melanogaster 239• H. sapiens 513
•A. thaliana 1000•O. sativa 1640•P. trichocarpa 2000+
Innate Immunity
Gene Duplications
Maize
Wheat
Rice
Brassica
Arabidopsis
Populus
CPK and PPCK
WAK14
4
6
25
31
Expanded families
Disease resistance
Self-incompatability
S locus RK
WAKL
WAK
Os Specific – lectin-like
SignalingCascades
Kinase Regulatory Systems
receptor
kinase cascade
Plant CIPK/CBL
MAPK Kinase Cascades
Caffrey et al (1999) J.Mol.Evol 49, 567-582.
Bioinformatics Group
• Gribskov Group• Staff• Emre Demiror• Hao Jiang• Ying Li
• Students• Omer Ahmad• Jin Tae Kwak• Kejie Li• Prasad Siddavatam• Reazur Rahman• Greg Ziegler
• San Diego Group• Fariba Fana• Degeng Wang• Sheila Podell• Jason Tchieu• Hannes Niedner
• Major Contributors• Douglas Smith• Jeff Harper• Catherine Chan• Alice Harmon• Estelle Hrabak• David Kerk• Shinhan Shiu
• Purdue Computational Genomics Facility
• Damion Junk• Doug Yatcilla
Aurora Kinases
Ste20 Family
Ste11 Family
3/3
Ste7 Family
MAPK
6/9
10/9
EssentialPhosphate
Maximal Linkage Clustering
Clustering
Clustering/Classification
• Pairwise distances• All-against-all BLAST
Uses entire sequence
Alignments not required
Longer matches, i.e. more domains, give better score
0
5000
10000
15000
20000
25000
0 10 20 30 40 50 60 70 80 90 100
110
120
130
140
150
160
170
180
-log( E-value )
Nu
mb
er
Nu
mb
er
BLASTDistance
Entire Sequence
BLASTDistance
Non-KinaseDomain