title: Actin cytoskeleton organization regulated by the PAK family of protein kinases.
abstract: 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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley 94720-3202, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Eby
authors.forename: S P
authors.initials: SP
authors.lastname: Holly
authors.forename: F
authors.initials: F
authors.lastname: van Drogen
authors.forename: A V
authors.initials: AV
authors.lastname: Grishin
authors.forename: M
authors.initials: M
authors.lastname: Peter
authors.forename: D G
authors.initials: DG
authors.lastname: Drubin
authors.forename: K J
authors.initials: KJ
authors.lastname: Blumer
mesh_terms: D000199:Actins / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity; D003599:Cytoskeleton / Q000201:enzymology / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013696:Temperature; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C095212:CLA4 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae