Actin cytoskeleton organization regulated by the PAK family of protein kinases

Cdc42, Rad and other Pho-type GTPases regulate gene expression, cell proliferation and cytoskeletal architecture [1,2]. A challenge is to identify the effecters of Cdc42 and Rad that mediate these biological responses. Protein kinases of the p21-activated kinase (PAK) family bind activated Rad 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 effecters of Cdc42 in pathways that regulate the organization of the cortical actin cytoskeleton.