Evolution of the Protein Kinase Family

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Evolution of the Protein Kinase Family

• Michael Gribskov

DEPARTMENT OF BIOLOGICAL SCIENCES
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Are Kinases PhosphoComputers?

• multiple sites AND or OR calculators

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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

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Signaling Cascades
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Protein Kinases

• Ser-Thr-Tyr Kinases are common to Eukaryotes
  (ePK)
• Two component Systems (Histidine Kinases)
• Bacteria (HK gtepK)
• Archaea (HK gtePK)
• Fungi (ePK gt HK)
• Animals (ePK gt HK)
• Plants (ePK gt HK)

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

• ePK?
• Pkn family
• ABC1 family
• RIO

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Core Protein Kinases

• Ubiquitous
• No extra domains
• Paradigms CK1, MAPK
• cell cycle
• meiosis/mitosis
• circadian cycle

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MAPK Cascades in Yeast
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Complex Kinases

• AGC family
• CAMK family
• Second messenger regulated
• Interact with regulatory subunits
• Frequently become fused

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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
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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

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

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

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Receptor Tyrosine Kinase Activation
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Complete Kinase Clustering
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Yeast Signaling (MAPK)
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Validating Transgenomic Predictions
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SnRK
 

• At AKIN10 and AKin11
• Rescue yeast SNF1 deletion
• Functional homolog

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Kinase Clustering and Classification

• Arabidopsis Rice
• Human
• Drosophila
• C. elegans
• Yeast

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PlantSpecific
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Protein Kinase Family Size

• Yeast 130
• C. elegans 454
• D. melanogaster 239
• H. sapiens 513

• A. thaliana 1000
• O. sativa 1640
• P. trichocarpa 2000

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Innate Immunity
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Gene Duplications
Maize
Wheat
Rice
Brassica
Arabidopsis
Populus
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CPK and PPCK
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WAK
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Expanded families

• Disease resistance
• Self-incompatability

WAK
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Os Specific lectin-like
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Signaling Cascades
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Kinase Regulatory Systems
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receptor
kinase cascade
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Plant CIPK/CBL
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MAPK Kinase Cascades
Caffrey et al (1999) J.Mol.Evol 49, 567-582.
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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

• Major Contributors
• Douglas Smith
• Jeff Harper
• Catherine Chan
• Alice Harmon
• Estelle Hrabak
• David Kerk
• Shinhan Shiu
• Purdue Computational Genomics Facility
• Damion Junk
• Doug Yatcilla

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Aurora Kinases
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Ste20 Family
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Ste11 Family
3/3
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Ste7 Family
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MAPK
6/9
10/9
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Essential Phosphate
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Clustering
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Clustering/Classification

• Pairwise distances
• All-against-all BLAST
• Uses entire sequence
• Alignments not required
• Longer matches, i.e. more domains, give better
  score

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BLASTDistance
Entire Sequence
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BLASTDistance
Non-KinaseDomain