SEARCH:   Advanced

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. Rameshwar Nuclear Factor-{kappa}B Accounts for the Repressor Effects of High Stromal Cell-Derived Factor-1{alpha} Levels on Tac1 Expression in Nontumorigenic Breast Cells Mol. Cancer Res., April 1, 2007; 5(4): 373 - 381. [Abstract] [Full Text] [PDF] J Kodama, Hasengaowa, T Kusumoto, N Seki, T Matsuo, Y Ojima, K Nakamura, A Hongo, and Y Hiramatsu Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer Ann. Onc., January 1, 2007; 18(1): 70 - 76. [Abstract] [Full Text] [PDF] T. Kawai, U. Choi, L. Cardwell, S. S. DeRavin, N. Naumann, N. L. Whiting-Theobald, G. F. Linton, J. Moon, P. M. Murphy, and H. L. Malech WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model engrafted with healthy human stem cells transduced with C-terminus-truncated CXCR4 Blood, January 1, 2007; 109(1): 78 - 84. [Abstract] [Full Text] [PDF] J. Sai, G. Walker, J. Wikswo, and A. Richmond The IL Sequence in the LLKIL Motif in CXCR2 Is Required for Full Ligand-induced Activation of Erk, Akt, and Chemotaxis in HL60 Cells J. Biol. Chem., November 24, 2006; 281(47): 35931 - 35941. [Abstract] [Full Text] [PDF] N. Michel, K. Ganter, S. Venzke, J. Bitzegeio, O. T. Fackler, and O. T. Keppler The Nef Protein of Human Immunodeficiency Virus Is a Broad-Spectrum Modulator of Chemokine Receptor Cell Surface Levels That Acts Independently of Classical Motifs for Receptor Endocytosis and G{alpha}i Signaling Mol. Biol. Cell, August 1, 2006; 17(8): 3578 - 3590. [Abstract] [Full Text] [PDF] M. Dagan-Berger, R. Feniger-Barish, S. Avniel, H. Wald, E. Galun, V. Grabovsky, R. Alon, A. Nagler, A. Ben-Baruch, and A. Peled Role of CXCR3 carboxyl terminus and third intracellular loop in receptor-mediated migration, adhesion and internalization in response to CXCL11 Blood, May 15, 2006; 107(10): 3821 - 3831. [Abstract] [Full Text] [PDF] S. Scala, P. Giuliano, P. A. Ascierto, C. Ierano, R. Franco, M. Napolitano, A. Ottaiano, M. L. Lombardi, M. Luongo, E. Simeone, et al. Human Melanoma Metastases Express Functional CXCR4 Clin. Cancer Res., April 15, 2006; 12(8): 2427 - 2433. [Abstract] [Full Text] [PDF] T. Florio, S. Casagrande, F. Diana, A. Bajetto, C. Porcile, G. Zona, S. Thellung, S. Arena, A. Pattarozzi, A. Corsaro, et al. Chemokine Stromal Cell-Derived Factor 1{alpha} Induces Proliferation and Growth Hormone Release in GH4C1 Rat Pituitary Adenoma Cell Line through Multiple Intracellular Signals Mol. Pharmacol., February 1, 2006; 69(2): 539 - 546. [Abstract] [Full Text] [PDF] B. M. Woerner, N. M. Warrington, A. L. Kung, A. Perry, and J. B. Rubin Widespread CXCR4 Activation in Astrocytomas Revealed by Phospho-CXCR4-Specific Antibodies Cancer Res., December 15, 2005; 65(24): 11392 - 11399. [Abstract] [Full Text] [PDF] E. Dalakas, P. N. Newsome, D. J. Harrison, and J. N. Plevris Hematopoietic stem cell trafficking in liver injury FASEB J, August 1, 2005; 19(10): 1225 - 1231. [Abstract] [Full Text] [PDF] M. Kucia, R. Reca, K. Miekus, J. Wanzeck, W. Wojakowski, A. Janowska-Wieczorek, J. Ratajczak, and M. Z. Ratajczak Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF-1-CXCR4 Axis Stem Cells, August 1, 2005; 23(7): 879 - 894. [Abstract] [Full Text] [PDF] M. Xu, E. Bruno, J. Chao, S. Huang, G. Finazzi, S. M. Fruchtman, U. Popat, J. T. Prchal, G. Barosi, R. Hoffman, et al. Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases Blood, June 1, 2005; 105(11): 4508 - 4515. [Abstract] [Full Text] [PDF] L. Wang, C. G. Radu, L. V. Yang, L. A. Bentolila, M. Riedinger, and O. N. Witte Lysophosphatidylcholine-induced Surface Redistribution Regulates Signaling of the Murine G Protein-coupled Receptor G2A Mol. Biol. Cell, May 1, 2005; 16(5): 2234 - 2247. [Abstract] [Full Text] [PDF] D. L. Hunton, W. G. Barnes, J. Kim, X.-R. Ren, J. D. Violin, E. Reiter, G. Milligan, D. D. Patel, and R. J. Lefkowitz {beta}-Arrestin 2-Dependent Angiotensin II Type 1A Receptor-Mediated Pathway of Chemotaxis Mol. Pharmacol., April 1, 2005; 67(4): 1229 - 1236. [Abstract] [Full Text] [PDF] S. Scala, A. Ottaiano, P. A. Ascierto, M. Cavalli, E. Simeone, P. Giuliano, M. Napolitano, R. Franco, G. Botti, and G. Castello Expression of CXCR4 Predicts Poor Prognosis in Patients with Malignant Melanoma Clin. Cancer Res., March 1, 2005; 11(5): 1835 - 1841. [Abstract] [Full Text] [PDF] B. Ahr, M. Denizot, V. Robert-Hebmann, A. Brelot, and M. Biard-Piechaczyk Identification of the Cytoplasmic Domains of CXCR4 Involved in Jak2 and STAT3 Phosphorylation J. Biol. Chem., February 25, 2005; 280(8): 6692 - 6700. [Abstract] [Full Text] [PDF] J. Sai, G.-H. Fan, D. Wang, and A. Richmond The C-terminal domain LLKIL motif of CXCR2 is required for ligand-mediated polarization of early signals during chemotaxis J. Cell Sci., November 1, 2004; 117(23): 5489 - 5496. [Abstract] [Full Text] [PDF] R. A. Colvin, G. S. V. Campanella, J. Sun, and A. D. Luster Intracellular Domains of CXCR3 That Mediate CXCL9, CXCL10, and CXCL11 Function J. Biol. Chem., July 16, 2004; 279(29): 30219 - 30227. [Abstract] [Full Text] [PDF] X. Wu, D.-J. Li, M.-M. Yuan, Y. Zhu, and M.-Y. Wang The Expression of CXCR4/CXCL12 in First-Trimester Human Trophoblast Cells Biol Reprod, June 1, 2004; 70(6): 1877 - 1885. [Abstract] [Full Text] [PDF] C. Liu, G. Sandford, G. Fei, and J. Nicholas G{alpha} Protein Selectivity Determinant Specified by a Viral Chemokine Receptor-Conserved Region in the C Tail of the Human Herpesvirus 8 G Protein-Coupled Receptor J. Virol., March 1, 2004; 78(5): 2460 - 2471. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020