SEARCH:   Advanced

Blood, 1 April 2008, Vol. 111, No. 7, pp. 3364-3372. Prepublished online as a Blood First Edition Paper on January 28, 2008; DOI 10.1182/blood-2007-08-106583. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-08-106583v1 111/7/3364    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 de Gorter, D. J. J. Articles by Spaargaren, M. Search for Related Content PubMed PubMed Citation Articles by de Gorter, D. J. J. Articles by Spaargaren, M. Related Collections Neoplasia Cell Adhesion and Motility Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS The small GTPase Ral mediates SDF-1–induced migration of B cells and multiple myeloma cells David J. J. de Gorter1, Rogier M. Reijmers1, Esther A. Beuling1, Hildegonda P. H. Naber1, Annemieke Kuil1, Marie José Kersten2, Steven T. Pals1, and Marcel Spaargaren1 Departments of1 Pathology and 2 Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Chemokine-controlled migration plays a critical role in B-cell development, differentiation, and function, as well as in the pathogenesis of B-cell malignancies, including the plasma cell neoplasm multiple myeloma (MM). Here, we demonstrate that stimulation of B cells and MM cells with the chemokine stromal cell–derived factor-1 (SDF-1) induces strong migration and activation of the Ras-like GTPase Ral. Inhibition of Ral, by expression of the dominant negative RalN28 mutant or of RalBPGAP, a Ral effector mutant that sequesters active Ral, results in impaired SDF-1–induced migration of B cells and MM cells. Of the 2 Ral isoforms, RalA and RalB, RalB was found to mediate SDF-1–induced migration. We have recently shown that Btk, PLC2, and Lyn/Syk mediate SDF-1–controlled B-cell migration; however, SDF-1–induced Ral activation is not affected in B cells deficient in these proteins. In addition, treatment with pharmacological inhibitors against PI3K and PLC or expression of dominant-negative Ras did not impair SDF-1–induced Ral activation. Taken together, these results reveal a novel function for Ral, that is, regulation of SDF-1–induced migration of B cells and MM cells, thereby providing new insights into the control of B-cell homeostasis, trafficking, and function, as well as into the pathogenesis of MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H.-T. Tsai, Y.-T. Tee, Y.-H. Hsieh, H.-L. Chiou, C.-W. Lin, H.-C. Tsai, P.-H. Wang, and S.-F. Yang Elevated Plasma Stromal Cell-derived Factor 1 Protein and its Gene Polymorphism in Patients With Pelvic Inflammatory Disease Reproductive Sciences, June 1, 2009; 16(6): 610 - 617. [Abstract] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020