Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin

Soosairajah, J; Maiti, S; Wiggan, O; Sarmiere, P; Moussi, N; Sarcevic, B; Sampath, R; Bamburg, JR; Bernard, O

Author(s): Soosairajah, J; Maiti, S; Wiggan, O; Sarmiere, P; Moussi, N; Sarcevic, B; Sampath, R; Bamburg, JR; Bernard, O;
Details: Publication Year 2005-02-09,Volume 24,Issue #3,Page 473-486
Journal Title: EMBO JOURNAL
Publication Type: Journal Article
Abstract: Slingshot (SSH) phosphatases and LIM kinases ( LIMK) regulate actin dynamics via a reversible phosphorylation ( inactivation) of serine 3 in actin-depolymerizing factor (ADF) and cofilin. Here we demonstrate that a multi-protein complex consisting of SSH-1L, LIMK1, actin, and the scaffolding protein, 14-3-3zeta, is involved, along with the kinase, PAK4, in the regulation of ADF/cofilin activity. Endogenous LIMK1 and SSH-1L interact in vitro and co- localize in vivo, and this interaction results in dephosphorylation and downregulation of LIMK1 activity. We also show that the phosphatase activity of purified SSH-1L is F-actin dependent and is negatively regulated via phosphorylation by PAK4. 14-3-3zeta binds to phosphorylated slingshot, decreases the amount of slingshot that co- sediments with F-actin, but does not alter slingshot activity. Here we define a novel ADF/cofilin phosphoregulatory complex and suggest a new mechanism for the regulation of ADF/cofilin activity in mediating changes to the actin cytoskeleton.
Publisher: NATURE PUBLISHING GROUP
Keywords: ACTIN DEPOLYMERIZING FACTOR; PROTEIN-KINASE; PHOSPHORYLATION; ACTIVATION; DYNAMICS; EXPRESSION; ROCK; RHO; REORGANIZATION; CYTOSKELETON
Publisher's Version: https://doi.org/10.1038/sj.emboj.7600543
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2005-02-09 12:00:00