Hsl7p, a Negative Regulator of Ste20p Protein Kinase in the Saccharomyces cerevisiae Filamentous Growth-Signaling Pathway

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-07, Vol.96 (15), p.8522-8527
• Main Authors: Fujita, Atsushi, Tonouchi, Akio, Hiroko, Takatoshi, Inose, Fumika, Nagashima, Takeyuki, Satoh, Rika, Tanaka, Shigeko
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Biological Sciences; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; Cell Cycle Proteins - metabolism; Cell Division - genetics; Cell growth; Developmental biology; Diploidy; Fungal Proteins - chemistry; Fungal Proteins - genetics; Gene Deletion; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Fungal; GTP-Binding Proteins - metabolism; Haploidy; Intracellular Signaling Peptides and Proteins; MAP Kinase Kinase Kinases; Molecular Sequence Data; Mutation; Nitrogen; Phenotype; Plasmids; Protein Binding; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Regulator genes; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins; Signal Transduction - genetics; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.15.8522

In the budding yeast, Saccharomyces cerevisiae, protein kinases Ste20p (p21Cdc42p/Rac-activated kinase), Ste11p [mitogen-activated protein kinase (MAPK) kinase kinase], Ste7p (MAPK kinase), Fus3p, and Kss1p (MAPKs) are utilized for haploid mating, invasive growth, and diploid filamentous growth. Members of the highly conserved Ste20p/p65PAK protein kinase family regulate MAPK signal transduction pathways from yeast to man. We describe here a potent negative regulator of Ste20p in the yeast filamentous growth-signaling pathway. We identified a mutant, hsl7, that exhibits filamentous growth on rich medium. Hsl7p belongs to a highly conserved protein family in eukaryotes. Hsl7p associates with the noncatalytic region within the amino-terminal half of Ste20p as well as Cdc42p. Deletions of HSL7 in haploid and diploid strains led to cell elongation and enhancement of both haploid invasive growth and diploid pseudohyphal growth. However, deletions of STE20 in haploid and diploid greatly diminished these hsl7-associated phenotypes. In addition, overexpression of HSL7 inhibited pseudohyphal growth. Thus, Hsl7p may inhibit the activity of Ste20p in the S. cerevisiae filamentous growth-signaling pathway. Our genetic analyses suggest the possibility that Cdc42p and Hsl7p compete for binding to Ste20p for pseudohyphal development when starved for nitrogen.