PMID:17189484

Citation	Heinrich, M, Köhler, T and Mösch, HU (2007) Role of Cdc42-Cla4 interaction in the pheromone response of Saccharomyces cerevisiae. Eukaryotic Cell 6:317-27
Abstract	In Saccharomyces cerevisiae, the highly conserved Rho-type GTPase Cdc42 is essential for cell division and controls cellular development during mating and invasive growth. The role of Cdc42 in mating has been controversial, but a number of previous studies suggest that the GTPase controls the mitogen-activated protein (MAP) kinase cascade by activating the p21-activated protein kinase (PAK) Ste20. To further explore the role of Cdc42 in pheromone-stimulated signaling, we isolated novel alleles of CDC42 that confer resistance to pheromone. We find that in CDC42(V36A) and CDC42(V36A, I182T) mutant strains, the inability to undergo pheromone-induced cell cycle arrest correlates with reduced phosphorylation of the mating MAP kinases Fus3 and Kss1 and with a decrease in mating efficiency. Furthermore, Cdc42(V36A) and Cdc42(V36A, I182T) proteins show reduced interaction with the PAK Cla4 but not with Ste20. We also show that deletion of CLA4 in a CDC42(V36A, I182T) mutant strain suppresses pheromone resistance and that overexpression of CLA4 interferes with pheromone-induced cell cycle arrest and MAP kinase phosphorylation in CDC42 wild-type strains. Our data indicate that Cla4 has the potential to act as a negative regulator of the mating pathway and that this function of the PAK might be under control of Cdc42. In conclusion, our study suggests that control of pheromone signaling by Cdc42 not only depends on Ste20 but also involves interaction of the GTPase with Cla4.
Links	PubMed PMC1797959 Online version:10.1128/EC.00102-06
Keywords	Cell Cycle; Drug Resistance, Fungal; Gene Expression Regulation, Fungal/drug effects; Intracellular Signaling Peptides and Proteins; MAP Kinase Signaling System/drug effects; Mitogen-Activated Protein Kinases; Peptides; Pheromones/pharmacology; Phosphorylation; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/growth & development; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Signal Transduction; Two-Hybrid System Techniques; beta-Galactosidase/metabolism; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae/metabolism
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