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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-06-1903. This Article Full Text (PDF) All Versions of this Article: 2002-06-1903v1 101/4/1308    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 McClure, B. J Articles by Lopez, A. F Search for Related Content PubMed PubMed Citation Articles by McClure, B. J Articles by Lopez, A. F Social Bookmarking                   What's this? Submitted June 27, 2002 Accepted September 10, 2002 Molecular assembly of the ternary granulocyte-macrophage colony-stimulating factor receptor complex Barbara J McClure, Timothy R Hercus, Bronwyn A Cambareri, Joanna M Woodcock, Christopher J Bagley, Geoff J Howlett, and Angel F Lopez* Cytokine Receptor Laboratory, Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, SA, Australia Protein Laboratory, Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, SA, Australia Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, Australia * Corresponding author; email: angel.lopez{at}imvs.sa.gov.au. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the production and functional activity of granulocytes and macrophages, properties that have encouraged its clinical use in bone marrow transplantation and in certain infectious diseases. Despite the importance of GM-CSF in regulating myeloid cell numbers and function little is known about the exact composition and mechanism of assembly of the GM-CSF receptor complex. We have now produced soluble forms of the GM-CSF receptor chain (sGMR) and ßchain (sßc) and utilised GM-CSF, the GM-CSF antagonist E21R and the ßc-blocking monoclonal antibody BION-1 to define the molecular assembly of the GM-CSF receptor complex. We found that GM-CSF and E21R were able to form low affinity, binary complexes with sGMR, each having a stoichiometry of 1:1. Importantly, GM-CSF but not E21R, formed a ternary complex with sGMRand sßc and this complex could be disrupted by E21R. Significantly, size exclusion chromatography, analytical ultracentrifugation and radioactive tracer experiments indicated that the ternary complex is composed of one sßc dimer with a single molecule each of sGMRand of GM-CSF. In addition, a hitherto unrecognised direct interaction between ßc and GM-CSF was detected which was absent with E21R and was abolished by BION-1. These results demonstrate a novel mechanism of cytokine receptor assembly likely to apply also to interleukin (IL) -3 and IL-5, and have implications for our molecular understanding and potential manipulation of GM-CSF activation of its receptor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Beekman, L. P. Verhagen, N. Geijsen, and P. J. Coffer Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output Blood, October 29, 2009; 114(18): 3917 - 3927. [Abstract] [Full Text] [PDF] T. R. Hercus, D. Thomas, M. A. Guthridge, P. G. Ekert, J. King-Scott, M. W. Parker, and A. F. Lopez The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease Blood, August 13, 2009; 114(7): 1289 - 1298. [Abstract] [Full Text] [PDF] M. L. Calicchio, T. Collins, and H. P. Kozakewich Identification of Signaling Systems in Proliferating and Involuting Phase Infantile Hemangiomas by Genome-Wide Transcriptional Profiling Am. J. Pathol., May 1, 2009; 174(5): 1638 - 1649. [Abstract] [Full Text] [PDF] M. Zaks-Zilberman, A. E. Harrington, T. Ishino, and I. M. Chaiken Interleukin-5 Receptor Subunit Oligomerization and Rearrangement Revealed by Fluorescence Resonance Energy Transfer Imaging J. Biol. Chem., May 9, 2008; 283(19): 13398 - 13406. [Abstract] [Full Text] [PDF] M. Brines, G. Grasso, F. Fiordaliso, A. Sfacteria, P. Ghezzi, M. Fratelli, R. Latini, Q.-w. Xie, J. Smart, C.-j. Su-Rick, et al. Erythropoietin mediates tissue protection through an erythropoietin and common {beta}-subunit heteroreceptor PNAS, October 12, 2004; 101(41): 14907 - 14912. [Abstract] [Full Text] [PDF] G. Ruggiero, G. Terrazzano, C. Becchimanzi, M. Sica, C. Andretta, A. M. Masci, L. Racioppi, B. Rotoli, S. Zappacosta, and F. Alfinito GPI-defective monocytes from paroxysmal nocturnal hemoglobinuria patients show impaired in vitro dendritic cell differentiation J. Leukoc. Biol., September 1, 2004; 76(3): 634 - 640. [Abstract] [Full Text] [PDF]

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