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Evolution of the Protein Kinase Family

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  1. Evolution of the Protein Kinase Family Michael Gribskov DEPARTMENT OF BIOLOGICAL SCIENCES

  2. Protein Kinase Protein Protein - P Protein Phosphatase

  3. Are Kinases PhosphoComputers? • multiple sites = AND or OR calculators X P P P OR P P AND X P

  4. 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

  5. Signaling Cascades

  6. 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)

  7. Archael ePKs Kennelly, P.J., (2003) Biochem. J. 379-389

  8. Bacterial ePKs • ePK? • Pkn family • ABC1 family • RIO

  9. Core Protein Kinases • Ubiquitous • No extra domains • Paradigms: CK1, MAPK • cell cycle • meiosis/mitosis • circadian cycle

  10. MAPK Cascades in Yeast

  11. Complex Kinases • AGC family • CAMK family • Second messenger regulated • Interact with regulatory subunits • Frequently become fused

  12. Protein Kinase Superfamily DD cAMP cAMP Regulatory Subunit PKA PKC PKG PKB cdk2 src EGFR Catalytic Subunit C1 C2 DD cGMP cGMP PH SH3 SH2 EGF Binding Domain Kinase Core

  13. 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

  14. Some Receptor Kinases (EGF receptor) (Insulin receptor) (FGF receptor)

  15. Receptor Kinases • Tyr-kinase in animals • Ser-Thr in plants • His in fungi and bacteria • Clearly the last role to evolve

  16. Receptor Tyrosine Kinase Activation

  17. Complete Kinase Clustering

  18. Yeast Signaling (MAPK)

  19. Validating Transgenomic Predictions

  20. 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 E=10-80 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 See Fig. 2 SnRK • At AKIN10 and AKin11 • Rescue yeast SNF1 deletion • Functional homolog

  21. Kinase Clustering and Classification • Arabidopsis & Rice • Human • Drosophila • C. elegans • Yeast

  22. CDC2 ? CDK7 PITSLRE CRK7 PlantSpecific

  23. Protein Kinase Family Size • Yeast 130 • C. elegans 454 • D. melanogaster 239 • H. sapiens 513 • A. thaliana 1000 • O. sativa 1640 • P. trichocarpa 2000+

  24. Innate Immunity

  25. Gene Duplications Maize Wheat Rice Brassica Arabidopsis Populus

  26. CPK and PPCK

  27. WAK 14 4 6 25 31

  28. WAKL S locus RK Expanded families Disease resistance Self-incompatability WAK

  29. Os Specific – lectin-like

  30. Signaling Cascades

  31. Kinase Regulatory Systems

  32. receptor kinase cascade

  33. Plant CIPK/CBL

  34. MAPK Kinase Cascades Caffrey et al (1999) J.Mol.Evol 49, 567-582.

  35. 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 Bioinformatics Group

  36. Aurora Kinases

  37. Ste20 Family