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

  • Mok, Janine Department of Molecular, Cellular, and Developmental Biology, Yale University, USA - Stanford Genome Technology Center, Department of Biochemistry, Stanford University, USA
  • Kim, Philip M. Department of Molecular Biophysics and Biochemistry, Yale University, USA - Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada
  • Lam, Hugo Y. K. Program in Computational Biology and Bioinformatics, Yale University, USA
  • Piccirillo, Stacy Department of Molecular, Cellular, and Developmental Biology, Yale University, USA
  • Zhou, Xiuqiong Department of Molecular, Cellular, and Developmental Biology, Yale University, USA
  • Jeschke, Grace R. Department of Pharmacology, Yale University School of Medicine, USA
  • Sheridan, Douglas L. Department of Pharmacology, Yale University School of Medicine, USA - Alexion Pharmaceuticals Inc., Cheshire, USA
  • Parker, Sirlester A. Department of Pharmacology, Yale University School of Medicine, USA
  • Desai, Ved Department of Pharmacology, Yale University School of Medicine, USA
  • Jwa, Miri Institute for Cellular and Molecular Biology, University of Texas, Austin, USA
  • Cameroni, Elisabetta Department of Medicine, Division of Biochemistry, University of Fribourg, Switzerland - Institute for Research in Biomedicine, Bellinzona, Switzerland
  • Niu, Hengyao Department of Biochemistry and Cell Biology, Stony Brook University, USA
  • Good, Matthew Department of Cellular and Molecular Pharmacology, University of California, San Francisco,USA
  • Remenyi, Attila Department of Cellular and Molecular Pharmacology, University of California, San Francisco,USA - Eötvös Loránd University, Department of Biochemistry, Budapest, Hungary
  • Ma, Jia-Lin Nianhan Department of Pathology, School of Medicine, Yale University, USA
  • Sheu, Yi-Jun Cold Spring Harbor Laboratory, Cold Spring Harbor, USA
  • Sassi, Holly E. Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada
  • Sopko, Richelle Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada
  • Chan, Clarence S. M. Institute for Cellular and Molecular Biology, University of Texas, Austin, USA
  • De Virgilio, Claudio Department of Medicine, Division of Biochemistry, University of Fribourg, Switzerland
  • Hollingsworth, Nancy M. Department of Biochemistry and Cell Biology, Stony Brook University, USA
  • Lim, Wendell A. Eötvös Loránd University, Department of Biochemistry and Howard Hughes Medical Institute, Budapest, Hungary
  • Stern, David F. Department of Pathology, School of Medicine, Yale University, USA
  • Stillman, Bruce Cold Spring Harbor Laboratory, Cold Spring Harbor, USA
  • Andrews, Brenda J. Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada
  • Gerstein, Mark B. Department of Molecular Biophysics and Biochemistry, Yale University, USA - Program in Computational Biology and Bioinformatics, Yale University, USA
  • Snyder, Michael Department of Molecular, Cellular, and Developmental Biology, Yale University, USA - Department of Molecular Biophysics and Biochemistry, Yale University, USA - Department of Genetics, Stanford University, Palo Alto, USA
  • Turk, Benjamin E. Department of Pharmacology, Yale University School of Medicine, USA
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    16.02.2010
Published in:
  • Science Signaling. - 2010, vol. 3, no. 109, p. ra12
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301588
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