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Mok J, et al.  (2010) Deciphering protein kinase specificity through large-scale analysis of yeast phosphorylation site motifs. Sci Signal 3(109):ra12

Abstract: Phosphorylation is a universal mechanism for regulating cell behavior in eukaryotes. Although protein kinases target short linear sequence motifs on their substrates, the rules for kinase substrate recognition are not completely understood. We used a rapid peptide screening approach to determine consensus phosphorylation site motifs targeted by 61 of the 122 kinases in Saccharomyces cerevisiae. By correlating these motifs with kinase primary sequence, we uncovered previously unappreciated rules for determining specificity within the kinase family, including a residue determining P-3 arginine specificity among members of the CMGC [CDK (cyclin-dependent kinase), MAPK (mitogen-activated protein kinase), GSK (glycogen synthase kinase), and CDK-like] group of kinases. Furthermore, computational scanning of the yeast proteome enabled the prediction of thousands of new kinase-substrate relationships. We experimentally verified several candidate substrates of the Prk1 family of kinases in vitro and in vivo and identified a protein substrate of the kinase Vhs1. Together, these results elucidate how kinase catalytic domains recognize their phosphorylation targets and suggest general avenues for the identification of previously unknown kinase substrates across eukaryotes.

Status: Published Type: Journal Article PubMed ID: 20159853

Topics addressed in this paper

Number of different genes curated to this paper: 63

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
ARK1 ATG1 BEM2 CAK1 CDC28 CDC7 CKA1 CLA4 CMK1 CMK2
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Topics Genes linked to topics (#11 - 20 )
DPB11 ECM29 EDE1 FUS3 GCN2 GIN4 GON7 GPH1 HOG1 HSL1
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Topics Genes linked to topics (#21 - 30 )
IPL1 KCC4 KIN1 KIN2 KIN3 KSS1 LAS17 MET5 MGA1 MPS1
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Topics Genes linked to topics (#31 - 40 )
NCL1 NUP188 PCL1 PCL2 PFK26 PHO85 PRK1 PRR1 PSK2 RAD53
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Topics Genes linked to topics (#41 - 50 )
RMD1 RPL5 SAC3 SEC21 SEF1 SFB3 SKM1 SLA2 SNF1 SOL2
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Topics Genes linked to topics (#51 - 60 )
STE20 SYP1 TOS3 TRK1 UFO1 UTR1 VAS1 VHS1 YAK1 YAP1801
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Topics Genes linked to topics (#61 - 63 )
YCK1 YOR093C YPK1
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