Src family kinases in G_q- and G_i-coupled receptor signaling. (Ai) The G_q-coupled PAR-4 signals via the activation of phospholipase β (PLCβ), which hydrolyses PI4,5P₂ to the second messengers DAG and IP₃, which in turn activate serine/threonine PKC and facilitate Ca²⁺ mobilization, respectively. The SFK Fyn associates with PKCδ downstream of PLCβ, and they reciprocally activate one another. Increased Ca²⁺ concentration contributes to SFK activation. SFKs lie upstream of the PI3K/Akt pathway. (Aii) PAR-4 coupled to G_12/13 mediates platelet shape change via the RhoA/ROCK/MLC pathway. Fyn activated downstream of G_12/13 inhibits signaling via G_q-coupled PAR-4. (B) The Gi-coupled ADP receptor P2Y₁₂ signals by inhibiting adenylate cyclase/cAMP/protein kinase A (PKA) and G_βγ-mediated activation of PI3K/Akt. The SFKs Lyn and Fyn bind directly to the G_α subunit and play a critical role in initiating signaling via the PI3K/Akt pathway.