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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Actins / metabolism*
-
Calcium-Calmodulin-Dependent Protein Kinases / physiology
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / physiology*
-
Cell Polarity
-
Cytoskeleton / enzymology
-
Cytoskeleton / metabolism*
-
GTP-Binding Proteins / genetics
-
GTP-Binding Proteins / physiology*
-
Intracellular Signaling Peptides and Proteins
-
MAP Kinase Kinase Kinases
-
Mutation
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / physiology*
-
Recombinant Proteins
-
Saccharomyces cerevisiae / cytology*
-
Saccharomyces cerevisiae / enzymology
-
Saccharomyces cerevisiae / genetics
-
Saccharomyces cerevisiae Proteins*
-
Signal Transduction
-
Temperature
-
cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
Substances
-
Actins
-
Cell Cycle Proteins
-
Intracellular Signaling Peptides and Proteins
-
Recombinant Proteins
-
Saccharomyces cerevisiae Proteins
-
CLA4 protein, S cerevisiae
-
Protein Serine-Threonine Kinases
-
Calcium-Calmodulin-Dependent Protein Kinases
-
MAP Kinase Kinase Kinases
-
STE20 protein, S cerevisiae
-
GTP-Binding Proteins
-
cdc42 GTP-Binding Protein, Saccharomyces cerevisiae