A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Adaptor Proteins, Signal Transducing; Cell Cycle Proteins; Cell Differentiation; Cell Membrane; Cyclin-Dependent Kinases; Cyclins; Electrostatics; *G1 Phase; *MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Phosphorylation; Protein Structure, Tertiary; Repressor Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
Life Sciences | Medicine and Health Sciences
Yeast cells arrest in the G1 phase of the cell cycle upon exposure to mating pheromones. As cells commit to a new cycle, G1 CDK activity (Cln/CDK) inhibits signaling through the mating MAPK cascade. Here we show that the target of this inhibition is Ste5, the MAPK cascade scaffold protein. Cln/CDK disrupts Ste5 membrane localization by phosphorylating a cluster of sites that flank a small, basic, membrane-binding motif in Ste5. Effective inhibition of Ste5 signaling requires multiple phosphorylation sites and a substantial accumulation of negative charge, which suggests that Ste5 acts as a sensor for high G1 CDK activity. Thus, Ste5 is an integration point for both external and internal signals. When Ste5 cannot be phosphorylated, pheromone triggers an aberrant arrest of cells outside G1 either in the presence or absence of the CDK-inhibitor protein Far1. These findings define a mechanism and physiological benefit of restricting antiproliferative signaling to G1.
Rights and Permissions
Citation: Cell. 2007 Feb 9;128(3):519-31. Link to article on publisher's site
DOI of Published Version
Strickfaden, Shelly Catherine; Winters, Matthew J.; Ben-Ari, Giora; Lamson, Rachel E.; Tyers, Michael D.; and Pryciak, Peter M., "A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway" (2007). GSBS Student Publications. 1210.