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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 28, 2008 Accepted January 27, 2009 Interactions of platelet integrin IIb and 3 transmembrane domains in mammalian cell membranes and their role in integrin activation Chungho Kim, Tong-Lay Lau, Tobias S. Ulmer, and Mark H. Ginsberg* Department of Medicine, University of California San Diego, La Jolla, CA, United States Department of Biochemistry & Molecular Biology and Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States * Corresponding author; email: mhginsberg{at}ucsd.edu. Clustering and occupancy of platelet integrin IIb3 (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 transmembrane and cytoplasmic domains in integrin signaling however, efforts to directly identify these associations have met with varying and controversial results. Here we develop mini-integrin affinity capture and use it in combination with NMR spectroscopy to show preferential heterodimeric association of integrin IIb3 TMD-tails via specific TMD interactions in mammalian cell membranes and in lipid bicelles. Furthermore, charge reversal mutations at IIb(R995)3(D723) confirm a proposed salt bridge and show that it stabilizes the TMD-tail association and talin binding to the 3 tail, which activates the integrin, disrupts this association. These studies establish the preferential heterodimeric interactions of integrin IIb3 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: F. Saltel, E. Mortier, V. P. Hytonen, M.-C. Jacquier, P. Zimmermann, V. Vogel, W. Liu, and B. Wehrle-Haller New PI(4,5)P2- and membrane proximal integrin-binding motifs in the talin head control {beta}3-integrin clustering J. Cell Biol., November 30, 2009; 187(5): 715 - 731. [Abstract] [Full Text] [PDF] 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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