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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-05-1435. This Article Full Text (PDF) All Versions of this Article: 2003-05-1435v1 103/2/507    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 Brown, A. L Articles by Gonda, T. J Search for Related Content PubMed PubMed Citation Articles by Brown, A. L Articles by Gonda, T. J Social Bookmarking                   What's this? Submitted May 7, 2003 Accepted August 28, 2003 Constitutive mutants of the GM-CSF receptor reveal multiple pathways leading to myeloid cell survival, proliferation, and granulocyte-macrophage differentiation Anna L Brown, Michelle Peters, Richard J D'Andrea*, and Thomas J Gonda Department of Immunology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia; Department of Immunology, Child Health Research Institute, Adelaide, SA, Australia; Department of Paediatrics, University of Adelaide, Adelaide, SA, Australia * Corresponding author; email: richard.dandrea{at}adelaide.edu.au. Activation of the GM-CSF family of receptors promotes the survival, proliferation and differentiation of cells of the myeloid compartment. Several signalling pathways are activated downstream of the receptor however it is not clear how these induce specific biological outcomes. We have previously identified two classes of constitutively active mutants of the shared signalling subunit, hc, of the human GM-CSF/ IL-3/ IL-5 receptors that exhibit different modes of signalling. In a factor-dependent bi-potential myeloid cell line, FDB1, an activated mutant containing a substitution in the transmembrane domain (V449E) induces factor-independent proliferation and survival, while mutants in the extracellular domain induce factor-independent granulocyte-macrophage differentiation. Here we have used further mutational analysis to demonstrate that there are non-redundant functions for several regions of the cytoplasmic domain with regard to mediating proliferation, viability and differentiation which have not been revealed by previous studies with the wild-type GM-CSF receptor. This unique lack of redundancy has revealed an association of a conserved membrane-proximal region with viability signalling and a critical but distinct role for tyrosine 577 in the activities of each class of mutant. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Zhao, F. A. Owaidi, D. R Pattabiraman, E. Verrier, A. Tsykin, G. J. Goodall, P. Leo, and T. J Gonda Identification of Novel MYB Target Genes Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 3580 - 3580. [Abstract] A. Brown, D. Salerno, C. Wilkinson, M. Perugini, C. Kok, G. Goodall, P. Solomon, T. Gonda, and R. D'Andrea The GM-CSF Receptor Utilises Members of the Canonical Wnt-Signaling Pathway during Macrophage Differentiation Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 3856 - 3856. [Abstract] T. L. Bonfield, M. J. Thomassen, C. F. Farver, S. Abraham, M. T. Koloze, X. Zhang, D. M. Mosser, and D. A. Culver Peroxisome Proliferator-Activated Receptor-{gamma} Regulates the Expression of Alveolar Macrophage Macrophage Colony-Stimulating Factor J. Immunol., July 1, 2008; 181(1): 235 - 242. [Abstract] [Full Text] [PDF] J. Lee, Y. Kim, J. Lim, M. Kim, and K. Han G-CSF and GM-CSF Concentrations and Receptor Expression in Peripheral Blood Leukemic Cells from Patients with Chronic Myelogenous Leukemia Ann. Clin. Lab. Sci., January 1, 2008; 38(4): 331 - 337. [Abstract] [Full Text] [PDF] A. L. Brown, C. R. Wilkinson, S. R. Waterman, C. H. Kok, D. G. Salerno, S. M. Diakiw, B. Reynolds, H. S. Scott, A. Tsykin, G. F. Glonek, et al. Genetic regulators of myelopoiesis and leukemic signaling identified by gene profiling and linear modeling J. Leukoc. Biol., August 1, 2006; 80(2): 433 - 447. [Abstract] [Full Text] [PDF] H.-S. Suh, M.-O. Kim, and S. C. Lee Inhibition of Granulocyte-Macrophage Colony-Stimulating Factor Signaling and Microglial Proliferation by Anti-CD45RO: Role of Hck Tyrosine Kinase and Phosphatidylinositol 3-Kinase/Akt J. Immunol., March 1, 2005; 174(5): 2712 - 2719. [Abstract] [Full Text] [PDF]

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