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PARs use cofactors to regulate the specificity and rates of cleavage. (A) The current model of PAR4 activation on platelets. PAR1 serves as a cofactor to enhance the rate of PAR4 cleavage by thrombin. The PAR1-PAR4 cooperation is based on the model originally proposed for PAR3-PAR4 on mouse platelets by Nakanishi-Matsui et al.22 (B) PAR1 cleavage by APC requires the EPCR as a cofactor.
