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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. X. P. P. P. OR. P. P. AND. X. P. Kinase Roles.

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Evolution of the Protein Kinase Family

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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

X

P

P

P

OR

P

P

AND

X

P


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

PKA

PKC

PKG

PKB

cdk2

src

EGFR

Catalytic Subunit

C1 C2

DD cGMP cGMP

PH

SH3 SH2

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


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


Kinase Clustering and Classification

  • Arabidopsis & Rice

  • Human

  • Drosophila

  • C. elegans

  • Yeast


CDC2

?

CDK7

PITSLRE

CRK7

PlantSpecific


Protein Kinase Family Size

  • Yeast130

  • C. elegans454

  • D. melanogaster239

  • H. sapiens513

  • A. thaliana1000

  • O. sativa1640

  • P. trichocarpa2000+


Innate Immunity


Gene Duplications

Maize

Wheat

Rice

Brassica

Arabidopsis

Populus


CPK and PPCK


WAK

14

4

6

25

31


WAKL

S locus RK

Expanded families

Disease resistance

Self-incompatability

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.


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


Aurora Kinases


Ste20 Family


Ste11 Family

3/3


Ste7 Family


MAPK

6/9

10/9


Essential

Phosphate


Clustering


Clustering/Classification

  • Pairwise distances

    • All-against-all BLAST

      • Uses entire sequence

      • Alignments not required

      • Longer matches, i.e. more domains, give better score


BLASTDistance

Entire Sequence


BLASTDistance

Non-KinaseDomain


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