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Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2003-01-0213. This Article Full Text (PDF) All Versions of this Article: 2003-01-0213v1 102/7/2491    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 Butta, N. Articles by Parrilla, R. Search for Related Content PubMed PubMed Citation Articles by Butta, N. Articles by Parrilla, R. Social Bookmarking                   What's this? Submitted January 24, 2003 Accepted June 6, 2003 Disruption of the 3 663-687 disulfide bridge confers constitutive activity to 3 integrins Nora Butta, Elena G Arias-Salgado, Consuelo Gonzalez-Manchon, Milagros Ferrer, Susana Larrucea, Matilde S Ayuso, and Roberto Parrilla* Pathophysiology and Human Molecular Genetics, Centro Invest. Biol. (CSIC), Madrid, Madrid, Spain * Corresponding author; email: rparrilla{at}cib.csic.es. The platelet fibrinogen receptor, integrin IIb3, is a non-covalent heterodimer of glycoproteins GPIIb and GPIIIa. This work aimed at elucidating the role played by the carboxyterminal extracellular, transmembrane, and cytoplasmic regions of the glycoprotein 3 in the formation of functional complexes with subunits. Progressive carboxyterminal deletions of 3 revealed that surface exposure of IIb3 or v3 could not take place in the absence of the transmembrane domain of 3. In contrast, internal deletions (616 to 690) of the carboxyterminal regions of the 3 ectodomain led to surface exposure of constitutive active receptors in CHO cells, as indicated by the enhanced rate of cell adhesion to immobilized ligands and spontaneous binding to soluble fibrinogen or activation-dependent antibody PAC-1. The functional analysis of cysteine mutations within the 616-690 region of 3 or chimeric 3-7 subunits revealed that disruption of the C663-C687 disulfide bridge endows constitutive activity to the aIIbb3 receptor. It is concluded that the carboxyterminal tail of the 3 ectodomain, so called TD domain, is not essential for cell surface expression of 3 receptors. However, a basal, non-activated, low ligand affinity state of the 3 integrins demands a normal conformation of this domain. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Gresele, E. Falcinelli, S. Giannini, P. D'Adamo, A. D'Eustacchio, T. Corazzi, A. M. Mezzasoma, F. Di Bari, G. Guglielmini, L. Cecchetti, et al. Dominant inheritance of a novel integrin {beta}3 mutation associated with a hereditary macrothrombocytopenia and platelet dysfunction in two Italian families Haematologica, May 1, 2009; 94(5): 663 - 669. [Abstract] [Full Text] [PDF] R. Mor-Cohen, N. Rosenberg, M. Landau, J. Lahav, and U. Seligsohn Specific Cysteines in {beta}3 Are Involved in Disulfide Bond Exchange-dependent and -independent Activation of {alpha}IIb{beta}3 J. Biol. Chem., July 11, 2008; 283(28): 19235 - 19244. [Abstract] [Full Text] [PDF] P. Chaurasia, J. A. Aguirre-Ghiso, O. D. Liang, H. Gardsvoll, M. Ploug, and L. Ossowski A Region in Urokinase Plasminogen Receptor Domain III Controlling a Functional Association with {alpha}5beta1 Integrin and Tumor Growth J. Biol. Chem., May 26, 2006; 281(21): 14852 - 14863. [Abstract] [Full Text] [PDF] T. Kamata, M. Handa, Y. Sato, Y. Ikeda, and S. Aiso Membrane-proximal {alpha}/{beta} Stalk Interactions Differentially Regulate Integrin Activation J. Biol. Chem., July 1, 2005; 280(26): 24775 - 24783. [Abstract] [Full Text] [PDF] B. D. Adair, J.-P. Xiong, C. Maddock, S. L. Goodman, M. A. Arnaout, and M. Yeager Three-dimensional EM structure of the ectodomain of integrin {alpha}V{beta}3 in a complex with fibronectin J. Cell Biol., March 28, 2005; 168(7): 1109 - 1118. [Abstract] [Full Text] [PDF] J. J. Calvete Structures of Integrin Domains and Concerted Conformational Changes in the Bidirectional Signaling Mechanism of {alpha}IIb{beta}3 Experimental Biology and Medicine, September 1, 2004; 229(8): 732 - 744. [Abstract] [Full Text] [PDF] A. Chigaev, G. J. Zwartz, T. Buranda, B. S. Edwards, E. R. Prossnitz, and L. A. Sklar Conformational Regulation of {alpha}4{beta}1-Integrin Affinity by Reducing Agents: "INSIDE-OUT" SIGNALING IS INDEPENDENT OF AND ADDITIVE TO REDUCTION-REGULATED INTEGRIN ACTIVATION J. Biol. Chem., July 30, 2004; 279(31): 32435 - 32443. [Abstract] [Full Text] [PDF]

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