PMID- 25310241
OWN - NLM
STAT- MEDLINE
DCOM- 20150724
LR  - 20211021
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 3
DP  - 2014 Oct 13
TI  - Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity.
LID - 10.7554/eLife.04126 [doi]
LID - e04126
AB  - Protein kinases have evolved diverse specificities to enable cellular information 
      processing. To gain insight into the mechanisms underlying kinase 
      diversification, we studied the CMGC protein kinases using ancestral 
      reconstruction. Within this group, the cyclin dependent kinases (CDKs) and 
      mitogen activated protein kinases (MAPKs) require proline at the +1 position of 
      their substrates, while Ime2 prefers arginine. The resurrected common ancestor of 
      CDKs, MAPKs, and Ime2 could phosphorylate substrates with +1 proline or arginine, 
      with preference for proline. This specificity changed to a strong preference for 
      +1 arginine in the lineage leading to Ime2 via an intermediate with equal 
      specificity for proline and arginine. Mutant analysis revealed that a variable 
      residue within the kinase catalytic cleft, DFGx, modulates +1 specificity. 
      Expansion of Ime2 kinase specificity by mutation of this residue did not cause 
      dominant deleterious effects in vivo. Tolerance of cells to new specificities 
      likely enabled the evolutionary divergence of kinases.
FAU - Howard, Conor J
AU  - Howard CJ
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, 
      Berkeley, United States.
FAU - Hanson-Smith, Victor
AU  - Hanson-Smith V
AD  - Department of Microbiology and Immunology, University of California, San 
      Francisco, San Francisco, United States.
FAU - Kennedy, Kristopher J
AU  - Kennedy KJ
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, 
      Berkeley, United States.
FAU - Miller, Chad J
AU  - Miller CJ
AD  - Department of Pharmacology, Yale University School of Medicine, New Haven, United 
      States.
FAU - Lou, Hua Jane
AU  - Lou HJ
AD  - Department of Pharmacology, Yale University School of Medicine, New Haven, United 
      States.
FAU - Johnson, Alexander D
AU  - Johnson AD
AD  - Department of Microbiology and Immunology, University of California, San 
      Francisco, San Francisco, United States.
FAU - Turk, Benjamin E
AU  - Turk BE
AD  - Department of Pharmacology, Yale University School of Medicine, New Haven, United 
      States.
FAU - Holt, Liam J
AU  - Holt LJ
AUID- ORCID: 0000-0002-4002-0861
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, 
      Berkeley, United States.
LA  - eng
GR  - R01 GM105947/GM/NIGMS NIH HHS/United States
GR  - R01 GM037049/GM/NIGMS NIH HHS/United States
GR  - T32 GM007324/GM/NIGMS NIH HHS/United States
GR  - R01 GM104047/GM/NIGMS NIH HHS/United States
GR  - GM037049/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141013
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Cyclins)
RN  - 0 (Peptides)
RN  - 94ZLA3W45F (Arginine)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arginine/metabolism
MH  - Cyclins/metabolism
MH  - *Evolution, Molecular
MH  - Humans
MH  - Kinetics
MH  - Meiosis
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Peptides/chemistry/metabolism
MH  - Phosphorylation
MH  - *Phylogeny
MH  - Proline/metabolism
MH  - Protein Kinases/*metabolism
MH  - Saccharomyces cerevisiae/cytology/enzymology
MH  - Substrate Specificity
PMC - PMC4228266
OTO - NOTNLM
OT  - Ime2
OT  - S. cerevisiae
OT  - ancestral reconstruction
OT  - biochemistry
OT  - cyclin-dependent kinase
OT  - evolution
OT  - evolutionary biology
OT  - genomics
OT  - human
OT  - mouse
OT  - neurospora
OT  - phosphoregulatory networks
OT  - protein kinase
COIS- The authors declare that no competing interests exist.
EDAT- 2014/10/14 06:00
MHDA- 2015/07/25 06:00
PMCR- 2014/10/14
CRDT- 2014/10/14 06:00
PHST- 2014/07/23 00:00 [received]
PHST- 2014/10/09 00:00 [accepted]
PHST- 2014/10/14 06:00 [entrez]
PHST- 2014/10/14 06:00 [pubmed]
PHST- 2015/07/25 06:00 [medline]
PHST- 2014/10/14 00:00 [pmc-release]
AID - 04126 [pii]
AID - 10.7554/eLife.04126 [doi]
PST - epublish
SO  - Elife. 2014 Oct 13;3:e04126. doi: 10.7554/eLife.04126.