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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-03-0978. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-03-0978v1 101/2/399    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 Roland, J. Articles by Biard-Piechaczyk, M. Search for Related Content PubMed PubMed Citation Articles by Roland, J. Articles by Biard-Piechaczyk, M. Related Collections Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 January 2003, Vol. 101, No. 2, pp. 399-406 CHEMOKINES Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling Joachim Roland, Brendan J. Murphy, Barbara Ahr, Véronique Robert-Hebmann, Vincent Delauzun, Keith E. Nye, Christian Devaux, and Martine Biard-Piechaczyk From the Laboratoire Infections Rétrovirales et Signalisation Cellulaire CNRS UMR 5121, Institut de Biologie, Montpellier, France; St Bartholomew's and The Royal London School of Medicine and Dentistry, London, United Kingdom. The CXCR4 chemokine receptor is a Gi protein-coupled receptor that triggers multiple intracellular signals in response to stromal cell-derived factor 1 (SDF-1), including calcium mobilization and p44/42 extracellular signal-regulated kinases (ERK1/2). Transduced signals lead to cell chemotaxis and are terminated through receptor internalization depending on phosphorylation of the C terminus part of CXCR4. Receptor endocytosis is also required for some receptors to stimulate ERK1/2 and to migrate through a chemokine gradient. In this study, we explored the role played by the 3 intracellular loops (ICL1-3) and the C terminus domain of CXCR4 in SDF-1-mediated signaling by using human embryonic kidney (HEK)-293 cells stably expressing wild-type or mutated forms of CXCR4. ICL3 of CXCR4 is specifically involved in Gi-dependent signals such as calcium mobilization and ERK activation, but does not trigger CXCR4 internalization after SDF-1 binding, indicating that ERK phosphorylation is independent of CXCR4 endocytosis. Surprisingly, ICL2, with or without the aspartic acid, arginine, and tyrosine (DRY) motif, is dispensable for Gi signaling. However, ICL2 and ICL3, as well as the C terminus part of CXCR4, are needed to transduce SDF-1-mediated chemotaxis, suggesting that this event involves multiple activation pathways and/or cooperation of several cytoplasmic domains of CXCR4. © 2003 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: K. E Corcoran, A. Malhotra, C. A Molina, and P. Rameshwar Stromal-derived factor-1{alpha} induces a non-canonical pathway to activate the endocrine-linked Tac1 gene in non-tumorigenic breast cells J. Mol. Endocrinol., March 1, 2008; 40(3): 113 - 123. [Abstract] [Full Text] [PDF] W. Zhang, J.-M. Navenot, N. M. Frilot, N. Fujii, and S. C. Peiper Association of Nucleophosmin Negatively Regulates CXCR4-Mediated G Protein Activation and Chemotaxis Mol. Pharmacol., November 1, 2007; 72(5): 1310 - 1321. [Abstract] [Full Text] [PDF] K. E. Corcoran and P. 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