Hsl7p, a negative regulator of Ste20p protein kinase in the Saccharomyces cerevisiae filamentous growth-signaling pathway

Abstract

In the budding yeast, Saccharomyces cerevisiae, protein kinases Ste20p (p21 Cdc42p͞Rac -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 Ste20p͞ p65 PAK 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.

Schizosaccharomyces pombe Histone Acetyltransferase Mst1 (KAT5) Is an Essential Protein Required for Damage Response and Chromosome Segregation

“…The most frequently isolated two-hybrid clone was skb1 1 , which encodes an arginine methyltransferase, an ortholog of S. cerevisiae Hsl7 (Fujita et al 1999;Shulewitz et al 1999;Lee et al 2000). We observed no obvious genetic interactions between Dskb1 and mst1-L344S, in contrast to budding yeast where hsl7 and esa1 mutants have been shown to have synthetic interactions (Ruault and Pillus 2006).…”

Sensing, signalling and integrating physical processes during Saccharomyces cerevisiae invasive and filamentous growth

“…Overexpression of the G " cyclins CLN1 and CLN2 enhances filamentous and invasive growth, represses pheromone signalling, and results in phosphorylation of Ste20 (Fujita et al, 1999 ;Madhani et al, 1999 ;Oehlen & Cross, 1998). However, another study demonstrated that Cln1 and Cln2 act in parallel to the STE MAPK pathway during filamentous growth (Loeb et al, 1999).…”

“…However, another study demonstrated that Cln1 and Cln2 act in parallel to the STE MAPK pathway during filamentous growth (Loeb et al, 1999). Hsl7, a negative regulator of the Swe1 protein kinase, apparently also binds to Ste20 and Cdc42 (Fujita et al, 1999). HSL7 deletion induces cell elongation and filament formation in rich medium, but this phenotype is diminished by a STE20 deletion.…”

The genetics of Pak

“…The methyltransferase Hsl7 negatively regulates Ste20 function in this pathway. Hsl7 binds to the N-terminal region of Ste20, possibly competing with Cdc42 (Fujita et al, 1999). Interestingly, Skb1, a fission yeast homolog of Hsl7, has been shown to have the opposite effect: it positively modulates Pak1 function and binds to a site on Pak1 that is different from that which binds Cdc42 (Gilbreth et al, 1996).…”