Deciphering protein kinase specificity through large-scale analysis of yeast phosphorylation site motifs

Mok, J., Kim, P. M., Lam, H. Y. K., Piccirillo, S., Zhou, X., Jeschke, G. R., Sheridan, D. L., Parker, S. A., Desai, V., Jwa, M., Cameroni, E., Niu, H., Good, M., Remenyi, A., Ma, J. L. N., Sheu, Y. J., Sassi, H. E., Sopko, R., Chan, C. S. M., De Virgilio, C., Hollingsworth, N. M., Lim, W. A., Stern, D. F., Stillman, B., Andrews, B. J., Gerstein, M. B., Snyder, M., Turk, B. E. (2010) Deciphering protein kinase specificity through large-scale analysis of yeast phosphorylation site motifs. Science Signaling, 3 (109). ISSN 19450877 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/20159853
DOI: 10.1126/scisignal.2000482

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 kinasesubstrate 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. Copyright 2008 the American Association for the Advancement of Science; all rights reserved.

Item Type: Paper
Additional Information:
Uncontrolled Keywords: cyclin dependent kinase glycogen synthase kinase mitogen activated protein kinase protein kinase article enzyme active site enzyme phosphorylation enzyme specificity nonhuman priority journal Saccharomyces cerevisiae amino acid sequence chemistry enzymology metabolism molecular genetics phosphorylation Eukaryota Molecular Sequence Data Protein Kinases Substrate Specificity
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date Deposited: 06 Mar 2012 14:14
Last Modified: 20 Jun 2017 16:35
PMCID: PMC2846625
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25028

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving