Hs17p, a negative regulator of Ste20p protein kinase in the Saccharomyces cerevisiae filamentous growth-signaling pathway

In the budding yeast, Saccharomyces cerevisiae, protein kinases Ste20p (p21 (Cdc42p/Rac)-activated kinase), Ste11p [mitogen-activated protein kinase (M APK) kinase kinase], Ste7p (MAPK kinase), Fus3p, and Kss1p (MAPKs) are util ized for haploid mating, invasive growth, and diploid filamentous growth, M embers of the highly conserved Ste20p/p65(PAK) protein kinase family regula te MAPK signal transduction pathwaays from yeast to man. We describe here a potent negative regulator of Ste20p in the yeast filamentous growth-signal ing pathway. We identified a mutant, hsl7, that exhibits filamentous growth on rich medium. Hsl7p belongs to a highly conserved protein family in euka ryotes. Hsl7p associates with the noncatalytic region within the amino-term inal half of Ste20p as well as Cdc42p, Deletions of HSL7 in haploid and dip loid strains led to cell elongation and enhancement of both haploid invasiv e growth and diploid pseudohyphal growth. However, deletions of STE20 in ha ploid and diploid greatly diminished these hsl7-associated phenotypes. In a ddition, 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.