Transcript General
Evolution of the Protein Kinase Family Michael Gribskov DEPARTMENT OF BIOLOGICAL SCIENCES Protein Kinase Protein Protein - P Protein Phosphatase Are Kinases PhosphoComputers? • multiple sites = AND or OR calculators P X P P P OR P AND P X 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 Signaling Cascades 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 DD cAMP cAMP Regulatory Subunit Catalytic Subunit C1 DD cGMP PKA C2 PKC PKG PKB cdk2 cGMP PH SH3 SH2 src EGFR EGF Binding Domain Kinase Core 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 • E=10-80 At AKIN10 and AKin11 • Rescue yeast SNF1 deletion • Functional homolog See Fig. 2 50 GIN4/ERC47/CLA6/D9719.13/YDR507C KCC4/YCL024W HSL1/(SEL2)/NIK1/YKL453/YKL101W SNF1/CAT1/GLC2/CCR1/PAS14/HAF3/D 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 Kinase Clustering and Classification • • • • • Arabidopsis & Rice Human Drosophila C. elegans Yeast CDC2 Plant ? Specific CDK7 PITSLRE CRK7 Protein Kinase Family Size • • • • • • • Yeast C. elegans D. melanogaster H. sapiens 130 454 239 513 A. thaliana O. sativa P. trichocarpa 1000 1640 2000+ Innate Immunity Gene Duplications Maize Wheat Rice Brassica Arabidopsis Populus CPK and PPCK WAK 14 4 6 25 31 Expanded families Disease resistance Self-incompatability WAKL S locus RK WAK Os Specific – lectin-like Signaling Cascades 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 Essential Phosphate Clustering Maximal Linkage Clustering Clustering/Classification Pairwise distances • All-against-all BLAST Uses entire sequence Alignments not required Longer matches, i.e. more domains, give better score 25000 Number 20000 Number • 15000 10000 5000 0 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -log( E-value ) BLAST Distance Entire Sequence BLAST Distance Non-Kinase Domain