Schematic model of the mechanism of the modulation of platelet signaling by MMP-2. MMP-2, through the PEX domain, interacts with integrin α_IIbβ₃ on the platelet surface. This interaction facilitates the cleavage of the extracellular domain of PAR1 at the acid aspartic 39 N terminus. MMP-2 cleavage generates an N-terminal (³⁹DPR-TRAP) that interacting with the receptor pocket induces PAR1 biased signaling. In particular, MMP-2 activates the G_q pathway, inducing PAR1-dependent p38-MAPK phosphorylation, phospholipase C (PLC) activation, and Ca⁺² fluxes, and the G_12/13 pathway, inducing Rho kinase activation, but not the G_i pathway.