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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 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 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 Butta, N. Articles by Parrilla, R. Search for Related Content PubMed PubMed Citation Articles by Butta, N. Articles by Parrilla, R. Related Collections Cell Adhesion and Motility Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 October 2003, Vol. 102, No. 7, pp. 2491-2497 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Disruption of the 3 663-687 disulfide bridge confers constitutive activity to 3 integrins Nora Butta, Elena G. Arias-Salgado, Consuelo González-Manchón, Milagros Ferrer, Susana Larrucea, Matilde S. Ayuso, and Roberto Parrilla From the Department of Pathophysiology and Human Molecular Genetics, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain. The platelet fibrinogen receptor, integrin IIb3, is a noncovalent heterodimer of glycoproteins IIb and IIIa. This work was aimed at elucidating the role played by the carboxy-terminal extracellular, trans-membrane, and cytoplasmic regions of the glycoprotein 3 in the formation of functional complexes with subunits. Progressive carboxy-terminal deletions of 3 revealed that surface exposure of IIb3 or v3 could not occur in the absence of the transmembrane domain of 3. In contrast, internal deletions 616 to 690 of the carboxy-terminal regions of the 3 ectodomain led to surface exposure of constitu tive 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 to 690 region of 3 or chimeric 3-7 subunits revealed that disruption of the C663-C687 disulfide bridge endows constitutive activity to the IIb3 receptor. It is concluded that the carboxy-terminal tail of the 3 ectodomain, so-called tail domain (TD), is not essential for cell surface expression of 3 receptors. However, a basal, nonactivated, low ligand-affinity state of the 3 integrins demands a normal conformation of this domain. (Blood. 2003;102:2491-2497) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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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