Journal of Biological Chemistry
Volume 275, Issue 31, 4 August 2000, Pages 23998-24002
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MECHANISMS OF SIGNAL TRANSDUCTION
Expression and Function of the Mouse Collagen Receptor Glycoprotein VI Is Strictly Dependent on Its Association with the FcRγ Chain*

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Platelet glycoprotein (GP) VI has been proposed as the major collagen receptor for activation of human platelets. Human GPVI belongs to the immunoglobulin superfamily and is noncovalently associated with the FcRγ chain that is involved in signaling through the receptor. In mice, similar mechanisms seem to exist as platelets from FcRγ chain-deficient mice do not aggregate in response to collagen. However, the activating collagen receptor on mouse platelets has not been definitively identified. In the current study we examined the function and in vivo expression of GPVI in control and FcRγ chain-deficient mice with the first monoclonal antibody against GPVI (JAQ1). On wild type platelets, JAQ1 inhibited platelet aggregation induced by collagen but not PMA or thrombin. Cross-linking of bound JAQ1, on the other hand, induced aggregation of wild type but not FcRγ chain-deficient platelets. JAQ1 stained platelets and megakaryocytes from wild type but not FcRγ chain-deficient mice. Furthermore, JAQ1 recognized GPVI (approximately 60 kDa) in immunoprecipitation and Western blot experiments with wild type but not FcRγ chain-deficient platelets. These results strongly suggest that GPVI is the collagen receptor responsible for platelet activation in mice and demonstrate that the association with the FcRγ chain is critical for its expression and function.

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Published, JBC Papers in Press, May 23, 2000, DOI 10.1074/jbc.M003803200

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This work was supported in part by Grant Ni 556/2-1 (to B. N. and J. E. G.) from the Deutsche Forschungsgemeinschaft and the BAYER AG.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.