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Related Collections Immunobiology Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2002, Vol. 99, No. 12, pp. 4318-4325 CHEMOKINES Lck is required for stromal cell-derived factor 1 (CXCL12)-induced lymphoid cell chemotaxis Marit Inngjerdingen, Knut Martin Torgersen, and Azzam A. Maghazachi From the Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway. Stromal cell-derived factor 1 (CXCL12) induces chemotaxis of lymphocytes through its receptor CXCR4. We examined the role of nonreceptor tyrosine kinases in CXCL12-induced chemotaxis of T cells and natural killer (NK) cells. Damnacanthal, a specific Lck inhibitor, but not the Syk inhibitor piceatannol, inhibited CXCL12-induced chemotaxis of both lymphocyte subsets. Similarly, damnacanthal was shown to inhibit CXCL12-induced chemotaxis of the Jurkat T-cell line. Stimulating T and NK cells with CXCL12 increased both the tyrosine phosphorylation and the kinase activity of Lck. A direct involvement of Lck in CXCL12-induced chemotaxis was demonstrated in the Lck-deficient Jurkat-derived cell line JCaM1.6. Although JCaM1.6 cells express CXCR4, no significant migration was detected after CXCL12 stimulation. Reconstitution with wild-type Lck restored both CXCL12-induced chemotaxis and Lck activation. Furthermore, cotransfection of wild-type Lck with C-terminal Src kinase (Csk) into JCaM1.6 failed to restore the chemotactic response induced by CXCL12. Finally, by targeting critical residues in the Src homology-2 (SH2) or SH3 domains of Lck, we observed that the SH3 domain is important for the function of Lck in CXCL12-mediated chemotaxis. Together, these results suggest a role for Lck in CXCL12-induced signaling pathways leading to lymphocyte chemotaxis. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I.-W. Park and J. J. He HIV-1 Nef-mediated inhibition of T cell migration and its molecular determinants J. Leukoc. Biol., November 1, 2009; 86(5): 1171 - 1178. [Abstract] [Full Text] [PDF] O. D. Schneider, A. A. Weiss, and W. E. Miller Pertussis Toxin Signals through the TCR to Initiate Cross-Desensitization of the Chemokine Receptor CXCR4 J. Immunol., May 1, 2009; 182(9): 5730 - 5739. [Abstract] [Full Text] [PDF] M. C. Ghosh, D. Baatar, G. Collins, A. Carter, F. Indig, A. Biragyn, and D. D. Taub Dexamethasone augments CXCR4-mediated signaling in resting human T cells via the activation of the Src kinase Lck Blood, January 15, 2009; 113(3): 575 - 584. [Abstract] [Full Text] [PDF] S. N. 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