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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 Honda, S. Articles by Matsuzawa, Y. Search for Related Content PubMed PubMed Citation Articles by Honda, S. Articles by Matsuzawa, Y. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2001, Vol. 97, No. 1, pp. 175-182 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Ligand binding to integrin v3 requires tyrosine 178 in the v subunit Shigenori Honda, Yoshiaki Tomiyama, Nisar Pampori, Hirokazu Kashiwagi, Teruo Kiyoi, Satoru Kosugi, Seiji Tadokoro, Yoshiyuki Kurata, Sanford J. Shattil, and Yuji Matsuzawa From the Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, and the Department of Blood Transfusion, Osaka University Hospital, Osaka, Japan, and the Departments of Vascular Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA. Integrin v3 has been implicated in angiogenesis and other biological processes. However, the ligand-binding sites in v, a non-I-domain  subunit, remain to be identified. Recently in IIb, the other partner of the 3 subunit, several discontinuous residues important for ligand binding were identified in the predicted loops between repeats 2 and 3 (W3 4-1 loop) and within repeat 3 (W3 2-3 loop). Based on these findings, alanine-scanning mutagenesis in 293 cells was used to investigate the role of these loops (cysteine [C]142-C155 and glycine [G]172-G181) of v in ligand binding. Wild-type v3 was able to bind soluble fibrinogen following integrin activation either by 0.5 mM manganese dichloride (MnCl2) or a mutation of 3 threonine (T)562 to asparagine. However, mutation of tyrosine (Y)178 to alanine in the predicted G172-G181 loop of v abolished fibrinogen binding, and alanine (A) substitutions at adjacent residues phenylalanine (F)177 and tryptophan (W)179 had a similar effect. Cells expressing Y178Av also failed to bind to immobilized fibrinogen. Moreover, the Y178A mutation abolished the binding of WOW-1 Fab, a monovalent ligand-mimetic anti-v3 antibody, and the expression of 3 ligand-induced binding sites (LIBS) induced by arginine-glycine-aspartic acid-tryptophan (RGDW). In sharp contrast to the data obtained with IIb, none of the mutations in the predicted W3 4-1 loop in v impaired ligand binding. These results implicate v Y178 in ligand binding to v3, and they suggest that there are key structural differences in the adhesive ligand-binding sites of v3 and IIb3. © 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: A. M. Gonzalez, J. Claiborne, and J. C. R. Jones Integrin Cross-talk in Endothelial Cells Is Regulated by Protein Kinase A and Protein Phosphatase 1 J. Biol. Chem., November 14, 2008; 283(46): 31849 - 31860. [Abstract] [Full Text] [PDF] R. I. Litvinov, C. Nagaswami, G. Vilaire, H. Shuman, J. S. Bennett, and J. W. Weisel Functional and structural correlations of individual {alpha}IIb{beta}3 molecules Blood, December 15, 2004; 104(13): 3979 - 3985. [Abstract] [Full Text] [PDF] N. Katori, F. Szlam, J. H. Levy, and K. A. Tanaka A Novel Method to Assess Platelet Inhibition by Eptifibatide with Thrombelastograph(R) Anesth. Analg., December 1, 2004; 99(6): 1794 - 1799. [Abstract] [Full Text] [PDF] T. Kiyoi, Y. Tomiyama, S. Honda, S. Tadokoro, M. Arai, H. Kashiwagi, S. Kosugi, H. Kato, Y. Kurata, and Y. Matsuzawa A naturally occurring Tyr143Hisalpha IIb mutation abolishes alpha IIbbeta 3 function for soluble ligands but retains its ability for mediating cell adhesion and clot retraction: comparison with other mutations causing ligand-binding defects Blood, May 1, 2003; 101(9): 3485 - 3491. [Abstract] [Full Text] [PDF] C. Ryckman, K. Vandal, P. Rouleau, M. Talbot, and P. A. Tessier Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion J. Immunol., March 15, 2003; 170(6): 3233 - 3242. [Abstract] [Full Text] [PDF] S. Tadokoro, Y. Tomiyama, S. Honda, H. Kashiwagi, S. Kosugi, M. Shiraga, T. Kiyoi, Y. Kurata, and Y. Matsuzawa Missense mutations in the beta 3 subunit have a different impact on the expression and function between alpha IIbbeta 3 and alpha vbeta 3 Blood, February 1, 2002; 99(3): 931 - 938. [Abstract] [Full Text] [PDF]

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