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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4747-4753. Prepublished online as a Blood First Edition Paper on February 13, 2009; DOI 10.1182/blood-2008-10-186551. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-10-186551v1 113/19/4747    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 Kim, C. Articles by Ginsberg, M. H. Search for Related Content PubMed PubMed Citation Articles by Kim, C. Articles by Ginsberg, M. H. Related Collections Platelets and Thrombopoiesis Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Interactions of platelet integrin IIb and β3 transmembrane domains in mammalian cell membranes and their role in integrin activation Chungho Kim1, Tong-Lay Lau2, Tobias S. Ulmer2, and Mark H. Ginsberg1 1 Department of Medicine, University of California San Diego, La Jolla; and 2 Department of Biochemistry and Molecular Biology and Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles Clustering and occupancy of platelet integrin IIbβ3 (GPIIb-IIIa) generate biologically important signals: conversely, intracellular signals increase the integrins' affinity, leading to integrin activation; both forms of integrin signaling play important roles in hemostasis and thrombosis. Indirect evidence implicates interactions between integrin and β transmembrane domains (TMDs) and cytoplasmic domains in integrin signaling; however, efforts to directly identify these associations have met with varying and controversial results. In this study, we develop mini-integrin affinity capture and use it in combination with nuclear magnetic resonance spectroscopy to show preferential heterodimeric association of integrin IIbβ3 TMD tails via specific TMD interactions in mammalian cell membranes in lipid bicelles. Furthermore, charge reversal mutations at IIb(R995)β3(D723) confirm a proposed salt bridge and show that it stabilizes the TMD-tail association; talin binding to the β3 tail, which activates the integrin, disrupts this association. These studies establish the preferential heterodimeric interactions of integrin IIbβ3 TMD tails in mammalian cell membranes and document their role in integrin signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Yang, Y.-Q. Ma, R. C. Page, S. Misra, E. F. Plow, and J. Qin Structure of an integrin {alpha}IIb{beta}3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation PNAS, October 20, 2009; 106(42): 17729 - 17734. [Abstract] [Full Text] [PDF]

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