Article
- The EMBO Journal (2007) 26, 4487 - 4500
- doi:10.1038/sj.emboj.7601847
Published online: 13 September 2007
Subject Categories:
Activation of the Cdc42p GTPase by cyclin-dependent protein kinases in budding yeast
Richelle Sopko1, Dongqing Huang1, Jeffrey C Smith2, Daniel Figeys2 and Brenda J Andrews1,3
- Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada
- Faculty of Medicine, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
- Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada
Correspondence to:
Brenda J Andrews, Molecular and Medical Genetics, University of Toronto, 160 College Street, CCBR, Room 1308, Toronto, Ontario, Canada M5S 3E1. Tel.: +1 416 978 8562; Fax: +1 416 946 8253; E-mail: brenda.andrews@utoronto.ca
Received 9 March 2007; Accepted 10 August 2007
Abstract
Cyclin-dependent kinases (CDKs) trigger essential cell cycle processes including critical events in G1 phase that culminate in bud emergence, spindle pole body duplication, and DNA replication. Localized activation of the Rho-type GTPase Cdc42p is crucial for establishment of cell polarity during G1, but CDK targets that link the Cdc42p module with cell growth and cell cycle commitment have remained largely elusive. Here, we identify the GTPase-activating protein (GAP) Rga2p as an important substrate related to the cell polarity function of G1 CDKs. Overexpression of RGA2 in the absence of functional Pho85p or Cdc28p CDK complexes is toxic, due to an inability to polarize growth. Mutation of CDK consensus sites in Rga2p that are phosphorylated both in vivo and in vitro by Pho85p and Cdc28p CDKs results in a loss of G1 phase-specific phosphorylation. A failure to phosphorylate Rga2p leads to defects in localization and impaired polarized growth, in a manner dependent on Rga2p GAP function. Taken together, our data suggest that CDK-dependent phosphorylation restrains Rga2p activity to ensure appropriate activation of Cdc42p during cell polarity establishment. Inhibition of GAPs by CDK phosphorylation may be a general mechanism to promote proper G1-phase progression.
Keywords:
- cell polarity,
- cyclin-dependent kinases,
- G1 phase,
- GTPase-activating proteins,
- phosphorylation
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Retinoid signalling in the development of the central nervous system
Nature Reviews Neuroscience Review (01 Nov 2002)
Plugging the GAP between cell polarity and cell cycle
EMBO reports Review (01 Jan 2008)
Multiple levels of cyclin specificity in cell-cycle control
Nature Reviews Molecular Cell Biology Review (01 Feb 2007)
RESEARCH
Phosphorylation of Bem2p and Bem3p may contribute to local activation of Cdc42p at bud emergence
The EMBO Journal Article (31 Oct 2007)
