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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 27, 2008 Accepted June 27, 2008 Identification of FcRIIa as the ITAM-bearing receptor mediating IIb3 outside-in integrin signaling in human platelets Brian Boylan, Cunji Gao, Vipul Rathore, Joan C. Gill, Debra K Newman, and Peter J. Newman* Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, United States Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States Department of Microbiology, Medical College of Wisconsin, Milwaukee, WI, United States The Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, United States * Corresponding author; email: peter.newman{at}bcw.edu. Immunoreceptor tyrosine-based activation motif (ITAM)-containing proteins have recently been demonstrated in macrophages and neutrophils to be required for cell surface integrins, following engagement of their ligands, to transmit activation signals into the cell. To identify ITAM-bearing proteins that mediate signaling via the platelet-specific integrin IIb3, 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 C (PLC)2. 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 that expressed a truncated 3 cytoplasmic domain. Taken together, these data suggest that ligand binding to platelet IIb3 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: M.-P. Gratacap, V. Martin, M.-C. Valera, S. Allart, C. Garcia, P. Sie, C. Recher, and B. Payrastre The new tyrosine-kinase inhibitor and anticancer drug dasatinib reversibly affects platelet activation in vitro and in vivo Blood, August 27, 2009; 114(9): 1884 - 1892. [Abstract] [Full Text] [PDF] A. B. Herr and R. W. Farndale Structural Insights into the Interactions between Platelet Receptors and Fibrillar Collagen J. Biol. Chem., July 24, 2009; 284(30): 19781 - 19785. [Abstract] [Full Text] [PDF] 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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