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Blood, 15 January 2005, Vol. 105, No. 2, pp. 474-480. Prepublished online as a Blood First Edition Paper on September 2, 2004; DOI 10.1182/blood-2004-03-0843. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0843v1 105/2/474    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Okabe, S. Articles by Broxmeyer, H. E. Search for Related Content PubMed PubMed Citation Articles by Okabe, S. Articles by Broxmeyer, H. E. Related Collections Immunobiology Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES Stromal cell–derived factor-1/CXCL12–induced chemotaxis of T cells involves activation of the RasGAP-associated docking protein p62Dok-1 Seiichi Okabe, Seiji Fukuda, Young-June Kim, Masaru Niki, Louis M. Pelus, Kazuma Ohyashiki, Pier Paolo Pandolfi, and Hal E. Broxmeyer From the Department of Microbiology/Immunology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, and the Walther Cancer Institute, Indianapolis, IN; the Cancer Biology and Genetics Program and the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY; and the First Department of Internal Medicine, Tokyo Medical University, Japan. Events mediating stromal cell–derived factor-1 (SDF-1/CXCL12) chemotaxis of lymphocytes are not completely known. We evaluated intracellular signaling through RasGAP-associated protein p62Dok-1 (downstream of tyrosine kinase [Dok-1]) and associated proteins. SDF-1/CXCL12 stimulated Dok-1 tyrosine phosphorylation and association with RasGAP, adaptor protein p46Nck, and Crk-L in Jurkat T cells. The phosphorylation of Dok-1 was blocked by pretreatment of cells with the src kinase inhibitor PP2. Src kinase family member Lck was implicated. SDF-1/CXCL12 did not phosphorylate Dok-1 in J.CaM1.6 cells, a Jurkat derivative not expressing Lck, but did phosphorylate Dok-1 in J.CaM1.6 cells expressing Lck. SDF-1/CXCL12 induced the tyrosine phosphorylation of Pyk2 and the association of Pyk2 with zeta chain–associated protein-70 kilodaltons (Zap-70) and Vav. SDF-1/CXCL12 enhanced the association of RasGAP with Pyk2. CXCR4–expressing NIH3T3 and Baf3 cells transfected with full-length Dok-1 cDNA were suppressed in their responses to SDF-1/CXCL12–induced chemotaxis; mitogen-activated protein (MAP) kinase activity was also decreased. Chemotaxis to SDF-1/CXCL12 was significantly enhanced in Dok-1–/– CD4+ and CD8+ splenic T cells. These results implicate Dok-1, Nck, Crk-L, and Src kinases—especially Lck, Pyk2, Zap-70, Vav, and Ras-GAP—in intracellular signaling by SDF-1/CXCL12, and they suggest that Dok-1 plays an important role in SDF-1/CXCL12–induced chemotaxis in T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] N. P. Smirnova, A. A. Ptitsyn, K. J. Austin, H. Bielefeldt-Ohmann, H. 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