HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 28, 29816-29820, July 9, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/28/29816    most recent M312848200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fischer, A. M. Articles by August, A. Search for Related Content PubMed PubMed Citation Articles by Fischer, A. M. Articles by August, A. Social Bookmarking                      What's this?

Regulation of CXC Chemokine Receptor 4-mediated Migration by the Tec Family Tyrosine Kinase ITK^*

Angela M. Fischer, Jason C. Mercer, Archana Iyer¶||, Melanie J. Ragin**, and Avery August¶

From the Immunology Research Laboratories and Department of Veterinary Science, Pathobiology Graduate Program, Department of Biochemistry and Molecular Biology, and the ^¶Immunobiology Option of the Integrated Bioscience Graduate Program, Pennsylvania State University, University Park, Pennsylvania 16802

Chemokines are critical in controlling lymphocyte traffic and migration. The CXC chemokine CXCL12/SDF-1 interacts with its receptor CXCR4 to induce the migration of a number of different cell types. Although an understanding of the physiological functions of this chemokine is emerging, the mechanism by which it regulates T cell migration is still unclear. We show here that the Tec family kinase ITK is activated rapidly following CXCL12/SDF-1 stimulation, and this requires Src and phosphatidylinositol 3-kinase activities. ITK regulates the ability of CXCL12/SDF-1 to induce T cell migration as overexpression of wild-type ITK-enhanced migration, and T cells lacking ITK exhibit reduced migration as well as adhesion in response to CXCL12/SDF-1. Further analysis suggests that ITK may regulate CXCR4-mediated migration and adhesion by altering the actin cytoskeleton, as ITK null T cells were significantly defective in CXCL12/SDF-1a-mediated actin polymerization. Our data suggest that ITK may regulate the ability of CXCR4 to induce T cell migration.

Received for publication, November 24, 2003 , and in revised form, April 23, 2004.

^* This work was supported by grants from the Johnson & Johnson Focused Giving Program, the American Heart Association (0330036N), and the National Institutes of Health (RO1-AI51626) (all to A. A.) and in part by a graduate student research grant from the College of Agricultural Sciences, Pennsylvania State University (to A. M. F.) and the Sloan Foundation (to M. J. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| Graduate fellow of the Huck Institutes for Life Sciences.

^** Sloan graduate fellow.

To whom correspondence should be addressed: Immunology Research Laboratories, Dept. of Veterinary Science, Pennsylvania State University, 115 Henning Bldg., University Park, PA 16802. Tel.: 814-863-3539; Fax: 814-863-6140; E-mail: axa45{at}psu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. A. Readinger, G. M. Schiralli, J.-K. Jiang, C. J. Thomas, A. August, A. J. Henderson, and P. L. Schwartzberg Selective targeting of ITK blocks multiple steps of HIV replication PNAS, May 6, 2008; 105(18): 6684 - 6689. [Abstract] [Full Text] [PDF]

				N. Sahu, C. Mueller, A. Fischer, and A. August Differential Sensitivity to Itk Kinase Signals for T Helper 2 Cytokine Production and Chemokine-Mediated Migration J. Immunol., March 15, 2008; 180(6): 3833 - 3838. [Abstract] [Full Text] [PDF]

				G. M. Fuhler, A. L. Drayer, S. G. M. Olthof, J. J. Schuringa, P. J. Coffer, and E. Vellenga Reduced activation of protein kinase B, Rac, and F-actin polymerization contributes to an impairment of stromal cell derived factor-1 induced migration of CD34+ cells from patients with myelodysplasia Blood, January 1, 2008; 111(1): 359 - 368. [Abstract] [Full Text] [PDF]

				L. Patrussi, C. Ulivieri, O. M. Lucherini, S. R. Paccani, A. Gamberucci, L. Lanfrancone, P. G. Pelicci, and C. T. Baldari p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells Blood, September 15, 2007; 110(6): 1730 - 1738. [Abstract] [Full Text] [PDF]

				D. Park, I. Park, D. Lee, Y. B. Choi, H. Lee, and Y. Yun The adaptor protein Lad associates with the G protein {beta} subunit and mediates chemokine-dependent T-cell migration Blood, June 15, 2007; 109(12): 5122 - 5128. [Abstract] [Full Text] [PDF]

				W. Tan, D. Martin, and J. S. Gutkind The G{alpha}13-Rho Signaling Axis Is Required for SDF-1-induced Migration through CXCR4 J. Biol. Chem., December 22, 2006; 281(51): 39542 - 39549. [Abstract] [Full Text] [PDF]

				M. Dagan-Berger, R. Feniger-Barish, S. Avniel, H. Wald, E. Galun, V. Grabovsky, R. Alon, A. Nagler, A. Ben-Baruch, and A. Peled Role of CXCR3 carboxyl terminus and third intracellular loop in receptor-mediated migration, adhesion and internalization in response to CXCL11 Blood, May 15, 2006; 107(10): 3821 - 3831. [Abstract] [Full Text] [PDF]

				L. D. Finkelstein, Y. Shimizu, and P. L. Schwartzberg Tec Kinases Regulate TCR-Mediated Recruitment of Signaling Molecules and Integrin-Dependent Cell Adhesion J. Immunol., November 1, 2005; 175(9): 5923 - 5930. [Abstract] [Full Text] [PDF]

				H. Kishimoto, Z. Wang, P. Bhat-Nakshatri, D. Chang, R. Clarke, and H. Nakshatri The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1{alpha}/CXCL12 Carcinogenesis, October 1, 2005; 26(10): 1706 - 1715. [Abstract] [Full Text] [PDF]

				S. D. Barbee and J. Alberola-Ila Phosphatidylinositol 3-Kinase Regulates Thymic Exit J. Immunol., February 1, 2005; 174(3): 1230 - 1238. [Abstract] [Full Text] [PDF]