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Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-06-1888. This Article Full Text (PDF) All Versions of this Article: 2003-06-1888v1 102/10/3658    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 Rathore, V. Articles by Newman, P. J Search for Related Content PubMed PubMed Citation Articles by Rathore, V. Articles by Newman, P. J Social Bookmarking                   What's this? Submitted June 13, 2003 Accepted July 28, 2003 PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets Vipul Rathore*, Michelle A Stapleton, Cheryl A Hillery, Robert R Montgomery, Timothy C Nichols, Elizabeth P Merricks, Debra K Newman, and Peter J Newman Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA Departments of Pediatrics, Microbiology, Pharmacology, Cellular Biology, and the Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA; Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA Department of Medicine, University of North Carolina, Chapel Hill, NC, USA Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA; Departments of Pediatrics, Microbiology, Pharmacology, Cellular Biology, and the Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA * Corresponding author; email: vrathore{at}bcsew.edu. Platelet adhesion at sites of vascular injury is mediated, in part, by interaction of the platelet plasma membrane GPIb/V/IX complex with von Willebrand Factor (VWF) presented on collagen-exposed surfaces. Recent studies indicate that GPIb/V/IX may be functionally coupled with the Fc receptor (FcR)-chain, which, by virtue of its cytoplasmic immunoreceptor tyrosine based activation motif, sends activation signals into the cell. PECAM-1 is an inhibitory receptor that has previously been shown to negatively regulate platelet responses to collagen, which transduces activation signals via the GPVI/FcR chain complex. To determine whether PECAM-1 might similarly regulate signals emanating from GPIb/FcR, we compared activation and aggregation responses to VWF of PECAM-1-positive and PECAM-1-deficient murine platelets. PECAM-1 and the FcR-chain became rapidly tyrosine phosphorylated in platelets following botrocetin-induced VWF binding, but FcR-chain tyrosine phosphorylation was delayed in PECAM-1-positive, versus PECAM-1-deficient platelets. PECAM-1-deficient platelets were hyper-aggregable to VWF, exhibited enhanced spreading, and, under conditions of arterial flow, formed markedly larger thrombi on immobilized VWF than did wild-type platelets. Taken together, these data support the notion that engagement of the GPIb complex, in addition to sending activation signals, also initiates a negative feedback loop involving PECAM-1 that controls the rate and extent of platelet activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Rivera, M. L. Lozano, L. Navarro-Nunez, and V. Vicente Platelet receptors and signaling in the dynamics of thrombus formation Haematologica, May 1, 2009; 94(5): 700 - 711. 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