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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4345-4352. Prepublished online as a Blood First Edition Paper on February 8, 2005; DOI 10.1182/blood-2004-07-2718. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2718v1 105/11/4345    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 Liu, J. Articles by Gartner, T. K. Search for Related Content PubMed PubMed Citation Articles by Liu, J. Articles by Gartner, T. K. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The 3 subunit of the integrin IIb3 regulates IIb-mediated outside-in signaling Junling Liu, Carl W. Jackson, Ralph A. Gruppo, Lisa K. Jennings, and T. Kent Gartner From the Department of Microbiology and Molecular Cell Sciences, University of Memphis, TN; Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, TN; Hematology-Oncology Department, Cincinnati Children's Hospital, OH; and Vascular Biology Center of Excellence, University of Tennessee Health Science Center, Memphis. Bidirectional signaling is an essential feature of IIb3 function. The IIb cytoplasmic domain negatively regulates 3-mediated inside-out signaling, but little is known about the regulation of IIb-mediated outside-in signaling. We show that IIb-mediated outside-in signaling is enhanced in platelets of a patient lacking the terminal 39 residues of the 3 cytoplasmic tail. This enhanced signaling was detected as thromboxane A2 (TxA2) production and granule secretion, and required ligand cross-linking of IIb3 and platelet aggregation. This outside-in signaling was specifically inhibited by a palmitoylated version of a 3 peptide corresponding to cytoplasmic domain residues R724-R734. Unlike the palmitoylated peptide, the nonpalmitoylated 3 peptide could not cross the platelet membrane and did not inhibit this outside-in signaling. The physiologic relevance of this 3-mediated negative regulation of IIb outside-in signaling was demonstrated in normal platelets treated with the palmitoylated peptide and a physiologic agonist. Binding of IIb3 complexes to immobilized peptides demonstrated that a peptide corresponding to 3 residues R724-R734 appears to bind to an IIb cytoplasmic domain peptide containing residues K989-D1002, but not to control peptides. These results demonstrate that IIb-mediated outside-in signaling resulting in TxA2 production and granule secretion is negatively regulated by a sequence of residues in the membrane distal 3 cytoplasmic domain sequence RKEFAKFEEER. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Su, J. Mi, J. Yan, P. Flevaris, Y. Lu, H. Liu, Z. Ruan, X. Wang, N. Kieffer, S. Chen, et al. RGT, a synthetic peptide corresponding to the integrin {beta}3 cytoplasmic C-terminal sequence, selectively inhibits outside-in signaling in human platelets by disrupting the interaction of integrin {alpha}IIb{beta}3 with Src kinase Blood, August 1, 2008; 112(3): 592 - 602. [Abstract] [Full Text] [PDF] G. R. Van de Walle, A. Schoolmeester, B. F. Iserbyt, J. M. E. M. Cosemans, J. W. M. Heemskerk, M. F. Hoylaerts, A. Nurden, K. Vanhoorelbeke, and H. Deckmyn Activation of {alpha}IIb{beta}3 is a sufficient but also an imperative prerequisite for activation of {alpha}2{beta}1 on platelets Blood, January 15, 2007; 109(2): 595 - 602. [Abstract] [Full Text] [PDF]

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