Delineation of the Ca²⁺-dependent signaling pathway mediating secretion in thrombin stimulated human platelets: calcineurin→Rac1→class II PAKs activation→cofilin dephosphorylation (bold, center). The PKC-dependent pathway (right) regulates secretion independently of Rac1-mediated pathway and through different target proteins. The second Rac1–stimulated pathway identified in this study activates PI3-kinases (left), which, through α_IIbβ₃ integrin activation, is involved in aggregate stabilization. PI3-kinase activity is partially regulated by secreted ADP through P2Y₁₂ receptor activation, which is independent of Rac1-mediated PI3-kinase activation.