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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-08-2452. This Article Full Text (PDF) All Versions of this Article: 2002-08-2452v1 101/12/4808    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 Rosenberg, N. Articles by Seligsohn, U. Search for Related Content PubMed PubMed Citation Articles by Rosenberg, N. Articles by Seligsohn, U. Social Bookmarking                   What's this? Submitted August 12, 2002 Accepted February 9, 2003 Major mutations in calf-1 And calf-2 domains of glycoprotein IIb in patients with Glanzmann thrombasthenia enable GPIIb/IIIa complex formation but impair its transport from the endoplasmic reticulum to the Golgi apparatus Nurit Rosenberg, Rivka Yatuv, Vladimir Sobolev, Hava Peretz, Ariella Zivelin, and Uri Seligsohn* Thrombosis and Hemostasis Research Institute, The Chaim Sheba Medical Center, Tel-Hashomer, Israel Weizmann Institute of Science, Department of Plant Sciences, Sackler Faculty of Medicine, Tel-Aviv University, Rehovot, Israel * Corresponding author; email: seligson{at}sheba.health.gov.il. The crystal structure of integrin v[beta]3 comprises three regions of contact between v and 3. The main contact on v is located in the -propeller while calf-1 and calf-2 domains contribute minor interfaces. Whether or not contacts between calf-1 and calf-2 domains of glycoprotein (GP)IIb (IIb) and GPIIIa (3) play a role in GPIIb/IIIa complex formation has not been established. In this study we analyzed the effects of two naturally occurring mutations in calf-1 and calf-2 domains on GPIIb/IIIa complex formation, its processing and transport to the cell membrane. The mutations investigated were a deletion-insertion in exon 25 located in calf-2 and an in-frame skipping of exon 20 located in calf-1. Mutated GPIIb cDNAs were co-transfected in baby hamster kidney cells with normal GPIIIa (3) cDNA. Analysis by flow cytometry failed to demonstrate detectable amounts of GPIIb or GPIIb/IIIa complex on the surface of cells transfected with each mutation, but immunohistochemical staining revealed their intracellular presence. GPIIb was mainly demonstrable as pro-GPIIb by immunoprecipitation of cell lysates expressing each mutation. Differential immunoflouresence staining of GPIIb and cellular organelles suggested that most altered complexes were located in the endoplasmic reticulum. Homology modeling of normal GPIIb based on the v3 crystal structure revealed similar contacts between v and 3, and IIb and 3. Introduction of the mutations into the model yielded partial disruption of the normal contacts in the corresponding domains. These data suggest that despite partial disruption of calf-1 or calf-2 domain GPIIb/IIIa complex is formed but its transport from the endoplasmic reticulum is impaired. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Vijapurkar, K. Ghosh, S. Shetty, M. A. McLane, A. M. Moura da Silva, and D. Butera A simple, novel and robust test to diagnose type I Glanzmann thrombasthenia Haematologica, May 1, 2008; 93(5): 797 - 798. [Full Text] [PDF] G. Losonczy, N. Rosenberg, Z. Boda, G. Vereb, J. Kappelmayer, H. Hauschner, Z. Bereczky, and L. Muszbek Three novel mutations in the glycoprotein IIb gene in a patient with type II Glanzmann thrombasthenia Haematologica, May 1, 2007; 92(5): 698 - 701. [Abstract] [Full Text] [PDF]

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