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This Article Full Text Full Text (PDF) 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 Bracke, M. Articles by Koenderman, L. Search for Related Content PubMed PubMed Citation Articles by Bracke, M. Articles by Koenderman, L. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2001, Vol. 97, No. 11, pp. 3478-3483 IMMUNOBIOLOGY Cytokine-induced inside-out activation of FcR (CD89) is mediated by a single serine residue (S263) in the intracellular domain of the receptor Madelon Bracke, Jan-Willem J. Lammers, Paul J. Coffer, and Leo Koenderman From the Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands. Fc receptors play an important role in leukocyte activation and the modulation of ligand binding ("activation") is a critical point of regulation. Previous studies demonstrated that the Fc receptor for IgA (FcRI/CD89) is regulated by cytokine stimulation, switching it to a high-binding state. To investigate the mechanism by which cytokine-induced signal transduction pathways result in FcRI activation, cell lines expressing various receptor mutants were generated. Binding studies indicated that truncation of the C-terminus of the FcRI resulted in constitutive IgA binding, removing the need for cytokine stimulation. Furthermore, mutagenesis of a single C-terminal serine residue (S263) to alanine (S>A) (single-letter amino acid codes) also resulted in constitutive IgA binding, whereas a serine to aspartate (S>D) mutation was no longer functional. The role of S263 might be in regulating the interaction with the cytoskeleton, because disruption of the cytoskeleton results in reduced IgA binding to both FcRwt and FcR_S>A. In addition, overexpression of a membrane-targeted intracellular domain of FcR, and the introduction of cell-permeable CD89 fusion proteins blocked IgA binding, implying a competition for endogenous proteins. The proposal is made that Fc receptors are activated by cytokines via an inside-out mechanism converging at the cytoplasmic tail of these receptors. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. ten Hove, L. A. Houben, J. A. M. Raaijmakers, L. Koenderman, and M. Bracke Rapid Selective Priming of Fc{alpha}R on Eosinophils by Corticosteroids J. Immunol., November 1, 2006; 177(9): 6108 - 6114. [Abstract] [Full Text] [PDF] J. E. Bakema, S. de Haij, C. F. den Hartog-Jager, J. Bakker, G. Vidarsson, M. van Egmond, J. G. J. van de Winkel, and J. H. W. Leusen Signaling through Mutants of the IgA Receptor CD89 and Consequences for Fc Receptor {gamma}-Chain Interaction J. Immunol., March 15, 2006; 176(6): 3603 - 3610. [Abstract] [Full Text] [PDF] J. M. Beekman, J. E. Bakema, J. van der Linden, B. Tops, M. Hinten, M. van Vugt, J. G. J. van de Winkel, and J. H. W. Leusen Modulation of Fc{gamma}RI (CD64) Ligand Binding by Blocking Peptides of Periplakin J. Biol. Chem., August 6, 2004; 279(32): 33875 - 33881. [Abstract] [Full Text] [PDF] J. M. Beekman, J. E. Bakema, J. G. J. van de Winkel, and J. H. W. Leusen Direct interaction between Fc{gamma}RI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity PNAS, July 13, 2004; 101(28): 10392 - 10397. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020