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Related Collections Cell Adhesion and Motility Signal Transduction Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2001, Vol. 97, No. 6, pp. 1727-1732 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Platelet endothelial cell adhesion molecule-1 serves as an inhibitory receptor that modulates platelet responses to collagen Sonali Patil, Debra K. Newman, and Peter J. Newman From the Blood Research Institute, The Blood Center of Southeastern Wisconsin, and the Departments of Microbiology and Molecular Genetics, Pharmacology, and Cellular Biology, Medical College of Wisconsin, Milwaukee, WI. Platelet responses to collagen are mediated by the combined actions of the integrin 21, which serves as a major collagen-binding receptor, and the GPVI/FcR-chain complex, which transmits collagen-specific activation signals into the cell interior through the action of an immunoreceptor tyrosine-based activation motif within the cytoplasmic domain of the FcR-chain. Despite much progress in identifying components of the signaling pathway responsible for collagen-induced platelet activation, virtually nothing is known about the regulatory elements that modulate this important hemostatic event. PECAM-1, a recently recognized member of the inhibitory receptor family, contains a functional immunoreceptor tyrosine-based inhibitory motif within its cytoplasmic domain that, when tyrosine phosphorylated, recruits and activates the protein-tyrosine phosphatase, SHP-2. To test the hypothesis that PECAM-1 functions to regulate GPVI/FcR-chain-mediated platelet activation, the responses of wild-type versus PECAM-1-deficient murine platelets to GPVI-specific agonists were compared. Four distinct GPVI/FcR-chain-dependent responses were found to be significantly exaggerated in platelets derived from PECAM-1-deficient mice, including Mg++-independent adhesion to immobilized fibrillar collagen, collagen-induced platelet aggregation, platelet aggregation induced by the GPVI-specific agonist collagen-related peptide, and GPVI/FcR-chain-induced dense granule secretion. Together, these data provide compelling evidence that PECAM-1 modulates platelet responses to collagen, and they implicate this novel member of the inhibitory receptor family in the regulation of primary hemostasis. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Bergom, C. Paddock, C. Gao, T. Holyst, D. K. Newman, and P. J. Newman An alternatively spliced isoform of PECAM-1 is expressed at high levels in human and murine tissues, and suggests a novel role for the C-terminus of PECAM-1 in cytoprotective signaling J. Cell Sci., April 15, 2008; 121(8): 1235 - 1242. [Abstract] [Full Text] [PDF] L. F. Brass, L. Zhu, and T. J. Stalker Novel Therapeutic Targets at the Platelet Vascular Interface Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): s43 - s50. [Abstract] [Full Text] [PDF] V. Randriamboavonjy, F. Pistrosch, B. Bolck, R. H.G. Schwinger, M. Dixit, K. Badenhoop, R. A. Cohen, R. Busse, and I. Fleming Platelet Sarcoplasmic Endoplasmic Reticulum Ca2+-ATPase and {micro}-Calpain Activity Are Altered in Type 2 Diabetes Mellitus and Restored by Rosiglitazone Circulation, January 1, 2008; 117(1): 52 - 60. [Abstract] [Full Text] [PDF] Y. Rui, X. Liu, N. Li, Y. Jiang, G. Chen, X. Cao, and J. 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