Eby J J, Holly S P, van Drogen F, Grishin A V, Peter M, Drubin D G, Blumer K J
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3202, USA.
Curr Biol. 1998 Aug 27;8(17):967-70. doi: 10.1016/s0960-9822(98)00398-4.
Cdc42, Rac1 and other Rho-type GTPases regulate gene expression, cell proliferation and cytoskeletal architecture [1,2]. A challenge is to identify the effectors of Cdc42 and Rac1 that mediate these biological responses. Protein kinases of the p21-activated kinase (PAK) family bind activated Rac1 and Cdc42, and switch on mitogen-activated protein (MAP) kinase pathways; however, their roles in regulating actin cytoskeleton organization have not been clearly established [3-5]. Here, we show that mutants of the budding yeast Saccharomyces cerevisiae lacking the PAK homologs Ste20 and Cla4 exhibit actin cytoskeletal defects, in vivo and in vitro, that resemble those of cdc42-1 mutants. Moreover, STE20 overexpression suppresses cdc42-1 growth defects and cytoskeletal defects in vivo, and Ste20 kinase corrects the actin-assembly defects of permeabilized cdc42-1 cells in vitro. Thus, PAKs are effectors of Cdc42 in pathways that regulate the organization of the cortical actin cytoskeleton.
Cdc42、Rac1及其他Rho型GTP酶调控基因表达、细胞增殖及细胞骨架结构[1,2]。一项挑战在于鉴定介导这些生物学反应的Cdc42和Rac1的效应蛋白。p21活化激酶（PAK）家族的蛋白激酶结合活化的Rac1和Cdc42，并开启丝裂原活化蛋白（MAP）激酶通路；然而，它们在调控肌动蛋白细胞骨架组织中的作用尚未明确[3-5]。在此，我们表明，缺乏PAK同源物Ste20和Cla4的芽殖酵母酿酒酵母突变体在体内和体外均表现出肌动蛋白细胞骨架缺陷，类似于cdc42-1突变体。此外，STE20过表达在体内抑制cdc42-1生长缺陷和细胞骨架缺陷，并且Ste20激酶在体外纠正通透化的cdc42-1细胞的肌动蛋白组装缺陷。因此，PAK是Cdc42在调控皮质肌动蛋白细胞骨架组织的通路中的效应蛋白。
