Actin cytoskeleton organization regulated by the PAK family of protein kinases

Curr Biol. 1998 Aug 27;8(17):967-70. doi: 10.1016/s0960-9822(98)00398-4.

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