Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase
- 1 June 1998
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 393 (6687), 805-809
- https://doi.org/10.1038/31729
Abstract
Cell division, cell motility and the formation and maintenance of specialized structures in differentiated cells depend directly on the regulated dynamics of the actin cytoskeleton1,2. To understand the mechanisms of these basic cellular processes, the signalling pathways that link external signals to the regulation of the actin cytoskeleton need to be characterized2,3. Here we identify a pathway for the regulation of cofilin, a ubiquitous actin-binding protein that is essential for effective depolymerization of actin filaments4,5,6,7,8. LIM-kinase 1, also known as KIZ, is a protein kinase with two amino-terminal LIM motifs9,10,11 that induces stabilization of F-actin structures in transfected cells. Dominant-negative LIM-kinase1 inhibits the accumulation of the F-actin. Phosphorylation experiments in vivo and in vitro provide evidence that cofilin is a physiological substrate of LIM-kinase 1. Phosphorylation by LIM-kinase 1 inactivates cofilin, leading to accumulation of actin filaments. Constitutively active Rac augmented cofilin phosphorylation and LIM-kinase 1 autophosphorylation whereas phorbol ester inhibited these processes. Our results define a mechanism for the regulation of cofilin and hence of actin dynamics in vivo. By modulating the stability of actin cytoskeletal structures, this pathway should play a central role in regulating cell motility and morphogenesis.Keywords
This publication has 18 references indexed in Scilit:
- Cofilin promotes rapid actin filament turnover in vivoNature, 1997
- Accelerating on a Treadmill: ADF/Cofilin Promotes Rapid Actin Filament Turnover in the Dynamic CytoskeletonThe Journal of cell biology, 1997
- Actin Depolymerizing Factor (ADF/Cofilin) Enhances the Rate of Filament Turnover: Implication in Actin-based MotilityThe Journal of cell biology, 1997
- Xenopus Actin Depolymerizing Factor/Cofilin (XAC) Is Responsible for the Turnover of Actin Filaments in Listeria monocytogenes TailsThe Journal of cell biology, 1997
- Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeletonCurrent Opinion in Cell Biology, 1997
- Actin dynamics in vivoCurrent Opinion in Cell Biology, 1997
- Actin-Based Cell Motility and Cell LocomotionCell, 1996
- Specificity of single LIM motifs in targeting and LIM/LIM interactions in situ.Genes & Development, 1996
- Identification and Characterization of a Novel Family of Serine/Threonine Kinases Containing Two N-terminal LIM MotifsPublished by Elsevier BV ,1995
- The ADF/Cofilin Proteins: Stimulus-responsive Modulators of Actin DynamicsMolecular Biology of the Cell, 1995