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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3284-3290. Prepublished online as a Blood First Edition Paper on December 14, 2006; DOI 10.1182/blood-2006-10-051664. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-10-051664v1 109/8/3284    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 Zou, Z. Articles by Kahn, M. L Search for Related Content PubMed PubMed Citation Articles by Zou, Z. Articles by Kahn, M. L Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 10, 2006 Accepted December 3, 2006 Structure-function analysis reveals discrete 3 integrin inside-out and outside-in signaling pathways in platelets Zhiying Zou, Hong Chen, Alec A Schmaier, Richard O Hynes, and Mark L Kahn* Division of Cardiology and Department of Medicine, University of Pennsylvania, Philadelphia, PA Center for Cancer Research, MIT, Cambridge, MA * Corresponding author; email: markkahn{at}mail.med.upenn.edu. A unique aspect of integrin receptor function is the transmission of bidirectional signals. In platelets IIbb3 integrins require "inside-out" signals to bind fibrinogen and form thrombi. Following ligand binding, IIbb3 integrins generate "outside-in" signals that contribute to thrombus stability. Since integrin cytoplasmic tails are short and lack enzymatic activity, bidirectional signals are believed to be mediated by interactions with intracellular proteins but the molecular basis for integrin signal transduction remains poorly understood. In the present study we have used retroviral vectors to express IIbb3 integrins with mutant 3 tails in mouse platelets and test mechanisms of bidirectional signaling. Using this approach we identify mutations, e.g. 3Y747A, that confer loss of signaling in both directions and others, e.g. 3T762A, that confer a selective loss of outside-in signals. These results reveal the presence of discrete bidirectional signaling pathways controlled by integrin subunits in platelets and describe a high-throughput means of further investigating these pathways in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Inside-out, outside-in: what's the difference? Edward F. Plow and Yan-Qing Ma Blood 2007 109: 3128-3129. [Full Text] [PDF] This article has been cited by other articles: R. Blue, M. A. Kowalska, J. Hirsch, M. Murcia, C. A. Janczak, A. Harrington, M. Jirouskova, J. Li, R. Fuentes, M. A. Thornton, et al. Structural and therapeutic insights from the species specificity and in vivo antithrombotic activity of a novel {alpha}IIb-specific {alpha}IIb{beta}3 antagonist Blood, July 2, 2009; 114(1): 195 - 201. [Abstract] [Full Text] [PDF] Z. Zou, A. A. Schmaier, L. Cheng, P. Mericko, S. K. Dickeson, T. P. Stricker, S. A. Santoro, and M. L. Kahn Negative regulation of activated {alpha}2 integrins during thrombopoiesis Blood, June 18, 2009; 113(25): 6428 - 6439. [Abstract] [Full Text] [PDF] A. J. Ablooglu, J. Kang, B. G. Petrich, M. H. Ginsberg, and S. J. Shattil Antithrombotic effects of targeting {alpha}IIb{beta}3 signaling in platelets Blood, April 9, 2009; 113(15): 3585 - 3592. [Abstract] [Full Text] [PDF] B. S. Coller and S. J. Shattil The GPIIb/IIIa (integrin {alpha}IIb{beta}3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend Blood, October 15, 2008; 112(8): 3011 - 3025. [Abstract] [Full Text] [PDF] M. Bouaouina, Y. Lad, and D. A. Calderwood The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate {beta}1 and {beta}3 Integrins J. Biol. Chem., March 7, 2008; 283(10): 6118 - 6125. [Abstract] [Full Text] [PDF] P. Flevaris, A. Stojanovic, H. Gong, A. Chishti, E. Welch, and X. Du A molecular switch that controls cell spreading and retraction J. Cell Biol., November 5, 2007; 179(3): 553 - 565. [Abstract] [Full Text] [PDF]

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