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

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Presentation on theme: "Evolution of the Protein Kinase Family Michael Gribskov DEPARTMENT OF BIOLOGICAL SCIENCES."— Presentation transcript:

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

2 Protein - PProtein Kinase Protein Phosphatase

3 DEPARTMENT OF BIOLOGICAL SCIENCES

4 Are Kinases PhosphoComputers? multiple sites = AND or OR calculators P P P P AND OR P X P X

5 DEPARTMENT OF BIOLOGICAL SCIENCES 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

6 Signaling Cascades

7 DEPARTMENT OF BIOLOGICAL SCIENCES 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)

8 DEPARTMENT OF BIOLOGICAL SCIENCES Archael ePKs Kennelly, P.J., (2003) Biochem. J. 379-389

9 DEPARTMENT OF BIOLOGICAL SCIENCES Bacterial ePKs ePK? Pkn family ABC1 family RIO

10 DEPARTMENT OF BIOLOGICAL SCIENCES Core Protein Kinases Ubiquitous No extra domains Paradigms: CK1, MAPK cell cycle meiosis/mitosis circadian cycle

11 DEPARTMENT OF BIOLOGICAL SCIENCES MAPK Cascades in Yeast

12 DEPARTMENT OF BIOLOGICAL SCIENCES Complex Kinases AGC family CAMK family Second messenger regulated Interact with regulatory subunits Frequently become fused

13 DEPARTMENT OF BIOLOGICAL SCIENCES Protein Kinase Superfamily PKA PKC PKG PKB cdk2 src EGFR Kinase Core Catalytic Subunit Regulatory Subunit DD cAMP cAMP SH3 SH2 PH C1 C2 EGF Binding Domain DD cGMP cGMP

14 DEPARTMENT OF BIOLOGICAL SCIENCES

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17 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

18 DEPARTMENT OF BIOLOGICAL SCIENCES Some Receptor Kinases (EGF receptor)(Insulin receptor)(FGF receptor)

19 DEPARTMENT OF BIOLOGICAL SCIENCES Receptor Kinases Tyr-kinase in animals Ser-Thr in plants His in fungi and bacteria Clearly the last role to evolve

20 DEPARTMENT OF BIOLOGICAL SCIENCES Receptor Tyrosine Kinase Activation

21 DEPARTMENT OF BIOLOGICAL SCIENCES Complete Kinase Clustering

22 DEPARTMENT OF BIOLOGICAL SCIENCES Yeast Signaling (MAPK)

23 DEPARTMENT OF BIOLOGICAL SCIENCES Validating Transgenomic Predictions

24 DEPARTMENT OF BIOLOGICAL SCIENCES SnRK At AKIN10 and AKin11 Rescue yeast SNF1 deletion Functional homolog

25 DEPARTMENT OF BIOLOGICAL SCIENCES Kinase Clustering and Classification Arabidopsis & Rice Human Drosophila C. elegans Yeast

26 DEPARTMENT OF BIOLOGICAL SCIENCES CDC2 ? CDK7 PITSLRE CRK7 Plant Specific

27 DEPARTMENT OF BIOLOGICAL SCIENCES Protein Kinase Family Size Yeast130 C. elegans454 D. melanogaster239 H. sapiens513 A. thaliana1000 O. sativa1640 P. trichocarpa2000+

28 DEPARTMENT OF BIOLOGICAL SCIENCES

29 Innate Immunity

30 DEPARTMENT OF BIOLOGICAL SCIENCES Gene Duplications Maize Wheat Rice Brassica Arabidopsis Populus

31 DEPARTMENT OF BIOLOGICAL SCIENCES CPK and PPCK

32 DEPARTMENT OF BIOLOGICAL SCIENCES WAK 14 4 6 25 31

33 DEPARTMENT OF BIOLOGICAL SCIENCES Expanded families Disease resistance Self-incompatability S locus RK WAKL WAK

34 DEPARTMENT OF BIOLOGICAL SCIENCES Os Specific – lectin-like

35 Signaling Cascades

36 DEPARTMENT OF BIOLOGICAL SCIENCES Kinase Regulatory Systems

37 DEPARTMENT OF BIOLOGICAL SCIENCES receptor kinase cascade

38 DEPARTMENT OF BIOLOGICAL SCIENCES

39

40

41 Plant CIPK/CBL

42 DEPARTMENT OF BIOLOGICAL SCIENCES

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

47 DEPARTMENT OF BIOLOGICAL SCIENCES

48 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

49 DEPARTMENT OF BIOLOGICAL SCIENCES Aurora Kinases

50 DEPARTMENT OF BIOLOGICAL SCIENCES Ste20 Family

51 DEPARTMENT OF BIOLOGICAL SCIENCES Ste11 Family 3/3

52 DEPARTMENT OF BIOLOGICAL SCIENCES Ste7 Family

53 DEPARTMENT OF BIOLOGICAL SCIENCES MAPK 6/9 10/9

54 DEPARTMENT OF BIOLOGICAL SCIENCES Essential Phosphate

55 DEPARTMENT OF BIOLOGICAL SCIENCES Clustering

56 DEPARTMENT OF BIOLOGICAL SCIENCES Clustering/Classification Pairwise distances All-against-all BLAST Uses entire sequence Alignments not required Longer matches, i.e. more domains, give better score

57 DEPARTMENT OF BIOLOGICAL SCIENCES BLAST Distance Entire Sequence

58 DEPARTMENT OF BIOLOGICAL SCIENCES BLAST Distance Non-Kinase Domain

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