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Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-12-3753. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3753v1 102/1/192    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 Ebner, K. Articles by Schmid, J. A. Search for Related Content PubMed PubMed Citation Articles by Ebner, K. Articles by Schmid, J. A. Related Collections Apoptosis Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 192-199 IMMUNOBIOLOGY GMCSF activates NF-B via direct interaction of the GMCSF receptor with IB kinase Karin Ebner, Alexander Bandion, Bernd R. Binder, Rainer de Martin, and Johannes A. Schmid From the Department of Vascular Biology and Thrombosis Research, University of Vienna and Competence Center Bio-Molecular Therapeutics, Vienna, Austria. Granulocyte-macrophage colony-stimulating factor (GMCSF) has a central role in proliferation and differentiation of hematopoetic cells. Furthermore, it influences the proliferation and migration of endothelial cells. GMCSF elicits these functions by activating a receptor consisting of a ligand-specific -chain and a -chain, which is common for GMCSF, interleukin-3 (IL-3), and IL-5. It is known that various signaling molecules such as Janus kinase 2 or transcription factors of the signal transducer and activator of transcription (STAT) family bind to the common -chain and initiate signaling cascades. However, -chain—specific signal transduction adapters have to be postulated given that IL-3, IL-5, and GMCSF induce partly distinct biologic responses. Using a yeast 2-hybrid system, we identified the -chain of the GMCSF receptor (GMR) as putative interaction partner of IB kinase , one of the central signaling kinases activating the transcription factor nuclear factor—B (NF-B). Using endogenous protein levels of endothelial cell extracts, we could verify the interaction by coimmunoprecipitation experiments. Fluorescence resonance energy transfer (FRET) microscopy confirmed the direct interaction of CFP-IKK and YFPGMR in living cells. Functional studies demonstrated GMCSF-dependent activation of IB kinase activity in endothelial cells, degradation of IB, and activation of NF-B. Further biologic studies using GMCSF-dependent TF-1 cells indicated that GMCSF-triggered activation of NF-B is important for cell survival and proliferation. (Blood. 2003;102:192-199) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Wang, J. D'Costa, C. I. Civin, and A. D. Friedman C/EBP{alpha} directs monocytic commitment of primary myeloid progenitors Blood, August 15, 2006; 108(4): 1223 - 1229. [Abstract] [Full Text] [PDF] J. Chen, J. M. Carcamo, and D. W. Golde The {alpha} Subunit of the Granulocyte-Macrophage Colony-stimulating Factor Receptor Interacts with c-Kit and Inhibits c-Kit Signaling J. Biol. Chem., August 4, 2006; 281(31): 22421 - 22426. [Abstract] [Full Text] [PDF] S.-Q. Wu and W. C. Aird Thrombin, TNF-{alpha}, and LPS exert overlapping but nonidentical effects on gene expression in endothelial cells and vascular smooth muscle cells Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H873 - H885. [Abstract] [Full Text] [PDF]

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