P2Y12R activation also recruits Gβγ subunits, causing phosphoinositide-3-kinase-(PI3K) dependent Akt phosphorylation and Rap1b activation, a key positive regulator pathway for the integrin GPIIb/IIIa. In this way, the sustained activation of P2Y12R contributes to thrombus stabilization. PI3Kβ isoform has been reported to be essential for ADP-induced TXA2 generation and platelet aggregation (Garcia et al., 2010) and to cooperate with PI3Kγ isoform in sustaining integrin activation (Cosemans et al., 2006; Schoenwaelder et al., 2007).