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Blood, 1 November 2005, Vol. 106, No. 9, pp. 2962-2968. Prepublished online as a Blood First Edition Paper on July 5, 2005; DOI 10.1182/blood-2005-02-0526. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-02-0526v1 106/9/2962    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 Berthebaud, M. Articles by Louache, F. Search for Related Content PubMed PubMed Citation Articles by Berthebaud, M. Articles by Louache, F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Chemokines, Cytokines, and Interleukins Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS RGS16 is a negative regulator of SDF-1–CXCR4 signaling in megakaryocytes Magali Berthebaud, Christel Rivière, Peggy Jarrier, Adlen Foudi, Yanyan Zhang, Daniel Compagno, Anne Galy, William Vainchenker, and Fawzia Louache From the Institut National de la Santé et de la Recherche Médicale (INSERM) U 362, Institut Gustave Roussy, Villejuif, France; and the Généthon, Evry, France. Regulators of G-protein signaling (RGS) constitute a family of proteins involved in the negative regulation of signaling through heterotrimeric G protein–coupled receptors (GPCRs). Several RGS proteins have been implicated in the down-regulation of chemokine signaling in hematopoietic cells. The chemokine stromal-cell–derived factor 1 (SDF-1) activates migration of hematopoietic progenitors cells but fails to activate mature megakaryocytes despite high levels of CXC chemokine receptor 4 (CXCR4) receptor expression in these cells. This prompted us to analyze RGS expression and function during megakaryocyte differentiation. We found that RGS16 and RGS18 mRNA expression was up-regulated during this process. Overexpressing RGS16 mRNA in the megakaryocytic MO7e cell line inhibited SDF-1–induced migration, mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) activation, whereas RGS18 overexpression had no effect on CXCR4 signaling. Knocking down RGS16 mRNA via lentiviral-mediated RNA interference increased CXCR4 signaling in MO7e cells and in primary megakaryocytes. Thus, our data reveal that RGS16 is a negative regulator of CXCR4 signaling in megakaryocytes. We postulate that RGS16 regulation is a mechanism that controls megakaryocyte maturation by regulating signals from the microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: RGS16 "tightens the reins" on CXCR4 Mariusz Z. Ratajczak Blood 2005 106: 2928-2929. [Full Text] [PDF] This article has been cited by other articles: M. H. Nisancioglu, W. M. Mahoney Jr., D. D. Kimmel, S. M. Schwartz, C. Betsholtz, and G. Genove Generation and Characterization of rgs5 Mutant Mice Mol. Cell. Biol., April 1, 2008; 28(7): 2324 - 2331. [Abstract] [Full Text] [PDF] S. Basu, N. T. Ray, S. J. Atkinson, and H. E. Broxmeyer Protein Phosphatase 2A Plays an Important Role in Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12-Mediated Migration and Adhesion of CD34+ Cells J. Immunol., September 1, 2007; 179(5): 3075 - 3085. [Abstract] [Full Text] [PDF] X. Hu, S. Dai, W.-J. Wu, W. Tan, X. Zhu, J. Mu, Y. Guo, R. Bolli, and G. Rokosh Stromal Cell Derived Factor-1{alpha} Confers Protection Against Myocardial Ischemia/Reperfusion Injury: Role of the Cardiac Stromal Cell Derived Factor-1{alpha} CXCR4 Axis Circulation, August 7, 2007; 116(6): 654 - 663. [Abstract] [Full Text] [PDF] Z. Chen, O. Naveiras, A. Balduini, A. Mammoto, M. A. Conti, R. S. Adelstein, D. Ingber, G. Q. Daley, and R. A. Shivdasani The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway Blood, July 1, 2007; 110(1): 171 - 179. [Abstract] [Full Text] [PDF] Z. Chen, M. Hu, and R. A. Shivdasani Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2 Blood, February 15, 2007; 109(4): 1451 - 1459. [Abstract] [Full Text] [PDF] P. von Hundelshausen and C. Weber Platelets as Immune Cells: Bridging Inflammation and Cardiovascular Disease Circ. Res., January 5, 2007; 100(1): 27 - 40. [Abstract] [Full Text] [PDF] S. Timmusk, C. Fossum, and M. Berg Porcine circovirus type 2 replicase binds the capsid protein and an intermediate filament-like protein. J. Gen. Virol., November 1, 2006; 87(Pt 11): 3215 - 3223. [Abstract] [Full Text] [PDF]

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