1. Departments of Physiology and Biochemistry & Biophysics, University of California, San Francisco, California 94143, USA
2. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA
3. Genomics Institute of the Novartis Foundation, San Diego, California 92121, USA

Correspondence to: David O. Morgan¹ Email: dmorgan@cgl.ucsf.edu

Abstract

The events of cell reproduction are governed by oscillations in the activities of cyclin-dependent kinases (Cdks)¹. Cdks control the cell cycle by catalysing the transfer of phosphate from ATP to specific protein substrates. Despite their importance in cell-cycle control, few Cdk substrates have been identified². Here, we screened a budding yeast proteomic library for proteins that are directly phosphorylated by Cdk1 in whole-cell extracts. We identified about 200 Cdk1 substrates, several of which are phosphorylated in vivo in a Cdk1-dependent manner. The identities of these substrates reveal that Cdk1 employs a global regulatory strategy involving phosphorylation of other regulatory molecules as well as phosphorylation of the molecular machines that drive cell-cycle events. Detailed analysis of these substrates is likely to yield important insights into cell-cycle regulation.