Article abstract
Nature Cell Biology 1, 253 - 259 (1999)
Published online: 28 July 1999 | doi:10.1038/12963
Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics
David C. Edwards1,5, Luraynne C. Sanders2,5, Gary M. Bokoch2 & Gordon N. Gill3,4
Abstract
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.
- Department of Chemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0650, USA
- Departments of Immunology and Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
- Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0650, USA
- e-mail: ggill@ucsd.edu
- These authors contributed equally to this work
Correspondence to: Gary M. Bokoch2 e-mail: bokoch@scripps.edu
