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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 5, 2004 Accepted September 1, 2004 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* Department of Microbiology/Immunology, Walther Oncology Center, and the Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, IN, USA Cancer Biology and Genetics Program, and Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan * Corresponding author; email: hbroxmey{at}iupui.edu. 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; phosphorylation of Dok-1 was blocked by pretreating cells with 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 phosphorylated Dok-1 in J.CaM1.6 cells expressing Lck. SDF-1/CXCL12 induced tyrosine phosphorylation of Pyk2, and association of Pyk2 with zeta chain associated protein-70 kilodaltons (Zap-70) and Vav. SDF-1/CXCL12 enhanced association of RasGAP with Pyk2. CXCR4-expressing NIH3T3 and Baf3 cells transfected with full length Dok-1 cDNA were suppressed in responsiveness to SDF-1/CXCL12-induced chemotaxis; 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, Src kinases, especially Lck, Pyk2, Zap-70, Vav, and Ras-GAP in intracellular signaling by SDF-1/CXCL12, and 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. Van Campen, H. Han, A. L. van Olphen, and T. R. 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