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

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Presentation transcript:

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

Protein - PProtein Kinase Protein Phosphatase

DEPARTMENT OF BIOLOGICAL SCIENCES

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

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

Signaling Cascades

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)

DEPARTMENT OF BIOLOGICAL SCIENCES Archael ePKs Kennelly, P.J., (2003) Biochem. J

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

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

DEPARTMENT OF BIOLOGICAL SCIENCES MAPK Cascades in Yeast

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

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

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

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

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

DEPARTMENT OF BIOLOGICAL SCIENCES Receptor Tyrosine Kinase Activation

DEPARTMENT OF BIOLOGICAL SCIENCES Complete Kinase Clustering

DEPARTMENT OF BIOLOGICAL SCIENCES Yeast Signaling (MAPK)

DEPARTMENT OF BIOLOGICAL SCIENCES Validating Transgenomic Predictions

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

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

DEPARTMENT OF BIOLOGICAL SCIENCES CDC2 ? CDK7 PITSLRE CRK7 Plant Specific

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

DEPARTMENT OF BIOLOGICAL SCIENCES

Innate Immunity

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

DEPARTMENT OF BIOLOGICAL SCIENCES CPK and PPCK

DEPARTMENT OF BIOLOGICAL SCIENCES WAK

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

DEPARTMENT OF BIOLOGICAL SCIENCES Os Specific – lectin-like

Signaling Cascades

DEPARTMENT OF BIOLOGICAL SCIENCES Kinase Regulatory Systems

DEPARTMENT OF BIOLOGICAL SCIENCES receptor kinase cascade

DEPARTMENT OF BIOLOGICAL SCIENCES

Plant CIPK/CBL

DEPARTMENT OF BIOLOGICAL SCIENCES

MAPK Kinase Cascades Caffrey et al (1999) J.Mol.Evol 49,

DEPARTMENT OF BIOLOGICAL SCIENCES

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

DEPARTMENT OF BIOLOGICAL SCIENCES Aurora Kinases

DEPARTMENT OF BIOLOGICAL SCIENCES Ste20 Family

DEPARTMENT OF BIOLOGICAL SCIENCES Ste11 Family 3/3

DEPARTMENT OF BIOLOGICAL SCIENCES Ste7 Family

DEPARTMENT OF BIOLOGICAL SCIENCES MAPK 6/9 10/9

DEPARTMENT OF BIOLOGICAL SCIENCES Essential Phosphate

DEPARTMENT OF BIOLOGICAL SCIENCES Clustering

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

DEPARTMENT OF BIOLOGICAL SCIENCES BLAST Distance Entire Sequence

DEPARTMENT OF BIOLOGICAL SCIENCES BLAST Distance Non-Kinase Domain