Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization

Nature. 1998 Jun 25;393(6687):809-12. doi: 10.1038/31735.

Abstract

Rac is a small GTPase of the Rho family that mediates stimulus-induced actin cytoskeletal reorganization to generate lamellipodia. Little is known about the signalling pathways that link Rac activation to changes in actin filament dynamics. Cofilin is known to be a potent regulator of actin filament dynamics, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3; however, the kinases responsible for this phosphorylation have not been identified. Here we show that LIM-kinase 1 (LIMK-1), a serine/threonine kinase containing LIM and PDZ domains, phosphorylates cofilin at Ser 3, both in vitro and in vivo. When expressed in cultured cells, LIMK-1 induces actin reorganization and reverses cofilin-induced actin depolymerization. Expression of an inactive form of LIMK-1 suppresses lamellipodium formation induced by Rac or insulin. Furthermore, insulin and an active form of Rac increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1 participates in Rac-mediated actin cytoskeletal reorganization, probably by phosphorylating cofilin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors
  • Actins / metabolism*
  • Actins / ultrastructure
  • Animals
  • COS Cells
  • Cell Membrane / drug effects
  • Cytoskeleton / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • GTP-Binding Proteins / metabolism
  • HeLa Cells
  • Humans
  • Insulin / pharmacology
  • Lim Kinases
  • Microfilament Proteins / metabolism*
  • Phosphorylation
  • Protein Kinases
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Signal Transduction
  • Transfection
  • rac GTP-Binding Proteins

Substances

  • Actin Depolymerizing Factors
  • Actins
  • DNA-Binding Proteins
  • Insulin
  • Microfilament Proteins
  • Protein Kinases
  • LIMK1 protein, human
  • Lim Kinases
  • Limk1 protein, rat
  • Protein-Serine-Threonine Kinases
  • GTP-Binding Proteins
  • rac GTP-Binding Proteins