CalDAG-GEFI and P2Y12 synergize in Cvx-dependent activation of Rap1 and ERK-MAPK. Washed WT or CalDAG-GEFI−/− (knockout [KO]) platelets were stimulated in standard aggregometry with (A) 100 ng/mL (low dose [LD]) or (B-C) 500 ng/mL (high dose [HD]) Cvx. Platelets were activated in the presence (C) of 75 μM 2-MesAMP to inhibit signaling by P2Y12. Rap1-GTP and phospho-ERK were determined in samples withdrawn at the indicated time points. Total ERK1/2 levels (bottom panel) were determined as a loading control. Results are representative of 3 individual experiments.