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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2780-2786. Prepublished online as a Blood First Edition Paper on July 18, 2008; DOI 10.1182/blood-2008-02-142125. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-142125v1 112/7/2780    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 Boylan, B. Articles by Newman, P. J. Search for Related Content PubMed PubMed Citation Articles by Boylan, B. Articles by Newman, P. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Identification of FcRIIa as the ITAM-bearing receptor mediating IIbβ3 outside-in integrin signaling in human platelets Brian Boylan1,*, Cunji Gao1,*, Vipul Rathore1, Joan C. Gill2, Debra K. Newman3,4, and Peter J. Newman1,46 1 Blood Research Institute, BloodCenter of Wisconsin, Milwaukee; and Departments of2 Pediatrics, 3 Microbiology, 4 Pharmacology, and 5 Cellular Biology and 6 The Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee Immunoreceptor tyrosine-based activation motif (ITAM)–containing proteins have recently been demonstrated in macrophages and neutrophils to be required for cell surface integrins to transmit activation signals into the cell. To identify ITAM-bearing proteins that mediate signaling via the platelet-specific integrin IIbβ3, fibrinogen binding was induced by (1) allowing platelets to spread directly on immobilized fibrinogen, or (2) activating the PAR1 thrombin receptor on platelets in suspension. Both initiated strong, ligand binding–dependent tyrosine phosphorylation of the ITAM-bearing platelet Fc receptor, FcRIIa, as well as downstream phosphorylation of the protein tyrosine kinase Syk and activation of phospholipase C2 (PLC2). Addition of Fab fragments of an FcRIIa-specific monoclonal antibody strongly inhibited platelet spreading on immobilized fibrinogen, as well as downstream tyrosine phosphorylation of FcRIIa, Syk, and PLC2, and platelets from a patient whose platelets express reduced levels of FcRIIa exhibited markedly reduced spreading on immobilized fibrinogen. Finally, fibrinogen binding–induced FcRIIa phosphorylation did not occur in human platelets expressing a truncated β3 cytoplasmic domain. Taken together, these data suggest that ligand binding to platelet IIbβ3 induces integrin cytoplasmic domain–dependent phosphorylation of FcRIIa, which then enlists selected components of the immunoreceptor signaling cascade to transmit amplification signals into the cell. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Tohyama and H. Yamamura Protein Tyrosine Kinase, Syk: A Key Player in Phagocytic Cells J. Biochem., March 1, 2009; 145(3): 267 - 273. [Abstract] [Full Text] [PDF]

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