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.
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Evolution of the Protein Kinase Family
Michael Gribskov
DEPARTMENT OF BIOLOGICAL SCIENCES
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Protein - PProtein
ProteinKinase
Protein Phosphatase
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Are Kinases PhosphoComputers?
• multiple sites = AND or OR calculators
P
P
P
PAND
OR
PX
PX
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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
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SignalingCascades
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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)
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Archael ePKs
Kennelly, P.J., (2003) Biochem. J. 379-389
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Bacterial ePKs
• ePK?
• Pkn family• ABC1 family• RIO
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Core Protein Kinases
• Ubiquitous• No extra domains• Paradigms: CK1, MAPK
• cell cycle• meiosis/mitosis• circadian cycle
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MAPK Cascades in Yeast
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Complex Kinases
• AGC family• CAMK family
• Second messenger regulated• Interact with regulatory subunits• Frequently become fused
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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
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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
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Some Receptor Kinases
(EGF receptor) (Insulin receptor) (FGF receptor)
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Receptor Kinases
• Tyr-kinase in animals• Ser-Thr in plants• His in fungi and bacteria
• Clearly the last role to evolve
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Receptor Tyrosine Kinase Activation
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Complete Kinase Clustering
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Yeast Signaling (MAPK)
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Validating Transgenomic Predictions
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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
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Kinase Clustering and Classification
• Arabidopsis & Rice• Human• Drosophila• C. elegans• Yeast
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CDC2
?
CDK7
PITSLRE
CRK7
PlantSpecific
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Protein Kinase Family Size
• Yeast 130• C. elegans 454• D. melanogaster 239• H. sapiens 513
•A. thaliana 1000•O. sativa 1640•P. trichocarpa 2000+
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Innate Immunity
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Gene Duplications
Maize
Wheat
Rice
Brassica
Arabidopsis
Populus
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CPK and PPCK
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WAK14
4
6
25
31
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Expanded families
Disease resistance
Self-incompatability
S locus RK
WAKL
WAK
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Os Specific – lectin-like
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SignalingCascades
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Kinase Regulatory Systems
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receptor
kinase cascade
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Plant CIPK/CBL
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MAPK Kinase Cascades
Caffrey et al (1999) J.Mol.Evol 49, 567-582.
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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
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Aurora Kinases
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Ste20 Family
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Ste11 Family
3/3
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Ste7 Family
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MAPK
6/9
10/9
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EssentialPhosphate
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Maximal Linkage Clustering
Clustering
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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
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BLASTDistance
Entire Sequence
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BLASTDistance
Non-KinaseDomain