Fujita A, Tonouchi A, Hiroko T, Inose F, Nagashima T, Satoh R, Tanaka S
National Institute of Bioscience and Human Technology, Agency of Industrial Science and Technology, 1-1 Higashi, Tsukuba 305-8566, Japan.
Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8522-7. doi: 10.1073/pnas.96.15.8522.
In the budding yeast, Saccharomyces cerevisiae, protein kinases Ste20p (p21(Cdc42p/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/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.
在出芽酵母酿酒酵母中，蛋白激酶Ste20p（p21（Cdc42p/Rac）激活激酶）、Ste11p[丝裂原活化蛋白激酶（MAPK）激酶激酶]、Ste7p（MAPK激酶）、Fus3p和Kss1p（MAPK）用于单倍体交配、侵袭性生长和二倍体丝状生长。高度保守的Ste20p/p65（PAK）蛋白激酶家族成员调节从酵母到人类的MAPK信号转导途径。我们在此描述酵母丝状生长信号通路中Ste20p的一种有效负调节因子。我们鉴定出一个突变体hsl7，它在丰富培养基上表现出丝状生长。Hsl7p属于真核生物中一个高度保守的蛋白家族。Hsl7p与Ste20p氨基末端一半的非催化区域以及Cdc42p结合。单倍体和二倍体菌株中HSL7的缺失导致细胞伸长，并增强单倍体侵袭性生长和二倍体假菌丝生长。然而，单倍体和二倍体中STE20的缺失极大地减少了这些与hsl7相关的表型。此外，HSL7的过表达抑制假菌丝生长。因此，Hsl7p可能在酿酒酵母丝状生长信号通路中抑制Ste20p的活性。我们的遗传分析表明，在氮饥饿时，Cdc42p和Hsl7p可能竞争与Ste20p结合以进行假菌丝发育。
