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Molecular and Cellular Biology, February 2002, p. 774-783, Vol. 22, No. 3
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.3.774-783.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Stromal Cell-Derived Factor 1{alpha} Activates LIM Kinase 1 and Induces Cofilin Phosphorylation for T-Cell Chemotaxis

Michiru Nishita,1 Hiroyuki Aizawa,2 and Kensaku Mizuno1*

Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan,1 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 212052

Received 9 July 2001/ Returned for modification 6 August 2001/ Accepted 15 October 2001

Stromal cell-derived factor 1 {alpha} (SDF-1{alpha}), the ligand for G-protein-coupled receptor CXCR4, is a chemotactic factor for T lymphocytes. LIM kinase 1 (LIMK1) phosphorylates cofilin, an actin-depolymerizing and -severing protein, at Ser-3 and regulates actin reorganization. We investigated the role of cofilin phosphorylation by LIMK1 in SDF-1{alpha}-induced chemotaxis of T lymphocytes. SDF-1{alpha} significantly induced the activation of LIMK1 in Jurkat human leukemic T cells and peripheral blood lymphocytes. SDF-1{alpha} also induced cofilin phosphorylation, actin reorganization, and activation of small GTPases, Rho, Rac, and Cdc42, in Jurkat cells. Pretreatment with pertussis toxin inhibited SDF-1{alpha}-induced LIMK1 activation, thus indicating that Gi protein is involved in LIMK1 activation. Expression of dominant negative Rac (DN-Rac), but not DN-Rho or DN-Cdc42, blocked SDF-1{alpha}-induced activation of LIMK1, which means that SDF-1{alpha}-induced LIMK1 activation is mediated by Rac but not by Rho or Cdc42. We used a cell-permeable peptide (S3 peptide) that contains the phosphorylation site (Ser-3) of cofilin to inhibit the cellular function of LIMK1. S3 peptide inhibited the kinase activity of LIMK1 in vitro. Treatment of Jurkat cells with S3 peptide inhibited the SDF-1{alpha}-induced cofilin phosphorylation, actin reorganization, and chemotactic response of Jurkat cells. These results suggest that the phosphorylation of cofilin by LIMK1 plays a critical role in the SDF-1{alpha}-induced chemotactic response of T lymphocytes.


* Corresponding author. Mailing address: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Aramaki-Aza-Aoba, Aoba-ku, Sendai 980-8578, Japan. Phone: 81-22-217-6676. Fax: 81-22-217-6678. E-mail: kmizuno{at}biology.tohoku.ac.jp.


Molecular and Cellular Biology, February 2002, p. 774-783, Vol. 22, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.3.774-783.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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