Fibrin stimulates tyrosine phosphorylation in a GPVI-dependent manner. Platelets from (Ai) human, (Aii) mice, (Bi) αIIb-deficient mice, and (Bii) GPVI-deficient mice were stimulated with thrombin (1 U/mL) or PAR-4 peptide (150 μM) in the presence of eptifibatide and, where shown, fibrinogen (200 μg/mL) and GPRP (5 μM). Stimulations were stopped after (A) 1 or (B) 3 minutes with the addition of 2× lysis buffer. A sample of the WCL was removed, and the remaining lysate was used to IP Syk. WCLs and IPs were separated by SDS-polyacrylamide gel electrophoresis and western blotted for pTyr, Syk, and the FcRγ chain, which coprecipitates with Syk. The results are shown as representative of 3 experiments.