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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5308-5317. Prepublished online as a Blood First Edition Paper on March 6, 2007; DOI 10.1182/blood-2007-01-067363. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-01-067363v1 109/12/5308    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 Kalesnikoff, J. Articles by Galli, S. J. Search for Related Content PubMed PubMed Citation Articles by Kalesnikoff, J. Articles by Galli, S. J. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Roles of RabGEF1/Rabex-5 domains in regulating FcRI surface expression and FcRI-dependent responses in mast cells Janet Kalesnikoff1, Eon J. Rios1, Ching-Cheng Chen1, M. Alejandro Barbieri2, Mindy Tsai1, See-Ying Tam1, and Stephen J. Galli1 1 Department of Pathology, Stanford University School of Medicine, Stanford, CA; 2 Department of Biological Sciences, Florida International University, College of Arts and Sciences, Miami, FL RabGEF1/Rabex-5, a guanine nucleotide exchange factor (GEF) for the endocytic pathway regulator, Rab5, contains a Vps9 domain, an A20-like zinc finger (ZnF) domain, and a coiled coil domain. To investigate the importance of these domains in regulating receptor internalization and cell activation, we lentivirally delivered RabGEF1 mutants into RabGEF1-deficient (–/–) mast cells and examined FcRI-dependent responses. Wild-type RabGEF1 expression corrected phenotypic abnormalities in –/– mast cells, including decreased basal FcRI expression, slowed FcRI internalization, elevated IgE + Ag–induced degranulation and IL-6 production, and the decreased ability of –/– cytosol to support endosome fusion. We showed that RabGEF1's ZnF domain has ubiquitin ligase activity. Moreover, the coiled coil domain of RabGEF1 is required for Rabaptin-5 binding and for maintaining basal levels of Rabaptin-5 and surface FcRI. However, mutants lacking either of these domains normalized phenotypic abnormalities in IgE + antigen–activated –/– mast cells. By contrast, correction of these –/– phenotypes required a functional Vps9 domain. Thus, FcRI-mediated mast cell functional activation is dependent on RabGEF1's GEF activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. A. McPherson, S. Everingham, R. Karisch, J. A. Smith, C. M. Udell, J. Zheng, Z. Jia, and A. W. B. Craig Contributions of F-BAR and SH2 Domains of Fes Protein Tyrosine Kinase for Coupling to the Fc{varepsilon}RI Pathway in Mast Cells Mol. Cell. Biol., January 15, 2009; 29(2): 389 - 401. [Abstract] [Full Text] [PDF] E. J. Rios, A. M. Piliponsky, C. Ra, J. Kalesnikoff, and S. J. Galli Rabaptin-5 regulates receptor expression and functional activation in mast cells Blood, November 15, 2008; 112(10): 4148 - 4157. [Abstract] [Full Text] [PDF]

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