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Blood, 29 October 2009, Vol. 114, No. 18, pp. 3917-3927. Prepublished online as a Blood First Edition Paper on August 4, 2009; DOI 10.1182/blood-2009-03-208850. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-03-208850v1 114/18/3917    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 CrossRef Google Scholar Articles by Beekman, J. M. Articles by Coffer, P. J. PubMed PubMed Citation Articles by Beekman, J. M. Articles by Coffer, P. J. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output Jeffrey M. Beekman1,2, Liesbeth P. Verhagen1, Niels Geijsen3, and Paul J. Coffer1,2 1 Molecular Immunology Laboratory, Department of Immunology, and 2 Department of Pediatric Immunology, Wilhelmina Childrens Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands; and 3 Harvard Stem Cell Institute, Massachusetts General Hospital, Center for Regenerative Medicine, Boston The granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)–3/IL-5 receptor family regulates the production and function of myeloid cells. These cytokines signal through receptor complexes that consist of unique ligand-binding -chains and common signaling β-chains. IL-5 is distinct from IL-3 and GM-CSF in its capacity to induce eosinophil development, however, the molecular mechanisms that generate functional diversity within this receptor family are mostly unknown. Here, we characterized the selective IL-5R–binding adapter protein syntenin in IL-5R function. Syntenin and IL-5R colocalize at the plasma membrane and in early endosomal compartments. Manipulation of syntenin expression by ectopic expression or knockdown selectively modulated IL-5R but not GM-CSF receptor signaling, and severely affected IL-5–induced eosinophil differentiation from primary human CD34+ hematopoietic progenitor cells. We found syntenin up-regulated during eosinophilopoiesis but down-regulated during neutropoiesis. Syntenin forms complexes with multiple IL-5R chains, suggesting that syntenin-enhanced IL-5R output may result from stabilization of an IL-5–induced oligomeric receptor complex. These data demonstrate that cytokine-specific functions can be transduced by unique receptor -chain–associating adapter proteins. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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