Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases

Research output: Contribution to journalArticle


Activating phosphorylation of cyclin-dependent protein kinases (CDKs) is necessary for their kinase activity and cell cycle progression. This phosphorylation is carried out by the Cdk-activating kinase (CAK); in contrast, little is known about the corresponding protein phosphatase. We show that type 2C protein phosphatases (PP2Cs) are responsible for this dephosphorylation of Cdc28p, the major budding yeast CDK. Two yeast PP2Cs, Ptc2p and Ptc3p, display Cdc28p phosphatase activity in vitro and in vivo, and account for ~90% of Cdc28p phosphatase activity in yeast extracts. Overexpression of PTC2 or PTC3 results in synthetic lethality in strains temperature-sensitive for yeast CAK1, and disruptions of PTC2 and PTC3 suppress the growth defect of a cak1 mutant. Furthermore, PP2C-like enzymes are the predominant phosphatases toward human Cdk2 in HeLa cell extracts, indicating that the substrate specificity of PP2Cs toward CDKs is evolutionarily conserved.


External organisations
  • Yale University
Research areas and keywords


  • Activating phosphorylation, Cdk-activating kinase (CAK), Cyclin-dependent kinase, Protein phosphatase type 2C
Original languageEnglish
Pages (from-to)2946-2957
JournalGenes and Development
Issue number22
Publication statusPublished - 1999 Dec 17
Publication categoryResearch
Externally publishedYes