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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 (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 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. Social Bookmarking                   What's this? Submitted March 29, 2002 Accepted August 21, 2002 Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling Joachim Roland, Brendan J Murphy, Barbara Ahr, Veronique Robert-Hebmann, Vincent Delauzun, Keith E Nye, Christian Devaux, and Martine Biard-Piechaczyk* Institut de Biologie, CNRS UMR 5121, Montpellier, France St Bartholomew's and The Royal London School of Medicine and Dentistry, London, United Kingdom * Corresponding author; email: piechacz{at}crbm.cnrs-mop.fr. The CXCR4 chemokine receptor is a Gi protein-coupled receptor that triggers multiple intracellular signals in response to 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 upon 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 three intracellular loops (ICL1-3) and the C terminus domain of CXCR4 in SDF-1-mediated signaling using human embryonic kidney (HEK)293 cells stably expressing wild type or mutated forms of CXCR4. ICL3 of CXCR4 is specifically involved in calcium mobilization and ERK activation, Gi-dependent signals, 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 DRY motif is dispensable for Gi signaling. However, ICL2, 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. 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. 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