Article
- The EMBO Journal (2005) 24, 473 - 486
- doi:10.1038/sj.emboj.7600543
Published online: 20 January 2005
Subject Categories:
Interplay between components of a novel LIM kinase–slingshot phosphatase complex regulates cofilin
Juliana Soosairajah1,4, Sankar Maiti2,4, O'Neil Wiggan2, Patrick Sarmiere2, Nathalie Moussi1, Boris Sarcevic3, Rashmi Sampath2, James R Bamburg2,5 and Ora Bernard1,5
- The Walter & Eliza Hall Institute of Medical Research, Victoria, Australia
- Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
- These authors contributed equally to the results presented in this manuscript
- Senior authors contributed equally to this work
Correspondence to:
James R Bamburg, Department of Biochemistry and Molecular Biology, Colorado State University, 235 MRB, Fort Collins, CO 80523-1870, USA. Tel.: +1 970 491 6096; Fax: +1 970 491 0494; E-mail: jbamburg@lamar.colostate.edu
Ora Bernard, Walter and Eliza Hall Medical Research, Parkville 3052, Victoria, Australia. Tel.: +61 39 345 2555; E-mail: bernard@wehi.edu.au
Received 12 March 2004; Accepted 10 December 2004
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, 14-3-3
, 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. 14-3-3 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.
Keywords:
- ADF/cofilin,
- LIMK1,
- PAK4,
- Slingshot,
- 14-3-3
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