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.
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
Nat. Cell Biol.
Date: Sep. 01, 1999
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