• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics.

Extracellular signals regulate actin dynamics through small GTPases of the Rho/Rac/Cdc42 (p21) family. Here we show that p21-activated kinase (Pak1) phosphorylates LIM-kinase at threonine residue 508 within LIM-kinase's activation loop, and increases LIM-kinase-mediated phosphorylation of the actin-regulatory protein cofilin tenfold in vitro. In vivo, activated Rac or Cdc42 increases association of Pak1 with LIM-kinase; this association requires structural determinants in both the amino-terminal regulatory and the carboxy-terminal catalytic domains of Pak1. A catalytically inactive LIM-kinase interferes with Rac-, Cdc42- and Pak1-dependent cytoskeletal changes. A Pak1-specific inhibitor, corresponding to the Pak1 autoinhibitory domain, blocks LIM-kinase-induced cytoskeletal changes. Activated GTPases can thus regulate actin depolymerization through Pak1 and LIM-kinase.

Pubmed ID: 10559936


  • Edwards DC
  • Sanders LC
  • Bokoch GM
  • Gill GN


Nature cell biology

Publication Data

September 6, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA58689
  • Agency: NIDDK NIH HHS, Id: DK13149
  • Agency: NIGMS NIH HHS, Id: GM39434

Mesh Terms

  • Actins
  • Animals
  • COS Cells
  • Cell Line
  • Cell Membrane
  • Cytoskeleton
  • Enzyme Activation
  • Humans
  • Kinetics
  • Lim Kinases
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Phosphothreonine
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Recombinant Proteins
  • Sequence Deletion
  • Signal Transduction
  • Transfection
  • Zinc Fingers
  • cdc42 GTP-Binding Protein
  • p21-Activated Kinases
  • rac GTP-Binding Proteins