FIGURE 9. Model of thrombin-induced platelet activation through PAR1 and PAR4.

Thrombin activates both PAR1 and PAR4 following vascular injury. PAR1 activates Gα_i/o, Gα_q, and Gα_12/13, whereas PAR4 activates Gα_q and Gα_12/13. All three of these G proteins play a role in platelet aggregation. Additionally, through secretion of the dense granules, ADP is released and acts as an autocrine signal on the P2Y₁₂ receptor. PAR4 signaling calcium mobilization downstream of phospholipase Cβ through the Gα_q pathway converges with signaling through the P2Y₁₂ pathway to induce platelet aggregation. Finally, Rap1 activation is partially dependent on P2Y₁₂ signaling but may also be activated directly through PAR1 or PAR4 most likely through signaling in the Gα_q or Gα_12/13 pathway.