Mechanism of thromboxane production and integrin αIIbβ3 activation after GPIb stimulation in human platelets. Stimulation of GPIb with VWF activates Src, which in turn causes successive activation of phospholipase Cγ2 (PLC2), MEK, and Erk. Erk activation by MEK-mediated phosphorylation activates phospholipase A2 (PLA2), leading to the liberation of arachidonic acid (AA) and its conversion to thromboxane A2 (TXA2) by cyclooxygenase (which is inhibited by aspirin). The released TXA2 then interacts with the G-protein–coupled TP receptor, whose stimulation ultimately contributes to GPIIb–IIIa activation and platelet aggregation. Dotted lines indicate the inhibitory action of various compounds against their respective targets. Note that Src-dependent PLCγ2 activation in response to VWF stimulation in platelets has been previously reported.^21,26