Regulation of Rap1 activation by CalDAG-GEFI and RASA3. Agonists binding to GPCRs of the Gq type or to ITAM-coupled receptors activate the PLC β or γ isoform to form IP3, which releases Ca²⁺ from stores. Ca²⁺ causes rapid CalDAG-GEFI–dependent Rap1 activation, which, through the cooperation of talin and kindlin-3, promotes the binding of adhesive proteins to α_IIbβ₃, enabling platelet aggregation. The process is regulated by RASA3, which hydrolyzes Rap1-GTP to inactive Rap-GDP. P2Y₁₂, the GPCR of the Gi type that binds ADP, inactivates RASA3, allowing sustained Rap1 signaling and full platelet aggregation. Professional illustration created by Somersault18:24.