EphB2 regulates platelet function through modulating calcium mobilization, PI3K- and integrin αIIbβ3-mediated signaling. EphB2 may directly and/or indirectly influence the activation of PLC isoforms and thereby controls PI3K signaling. The consequences of these signaling events modulate the calcium mobilization, integrin αIIbβ3 mediated inside-out signaling, and granule secretion. Because EphB2 is physically associated with integrin αIIbβ3, it may be involved in the regulation of integrin αIIbβ3 mediated outside-in signaling. α and δ in small discs represent α and dense granules, respectively. The dotted lines indicate the predictive functions. DAG, diacylglycerol; FCRγ, Fc receptor γ chain; GPCR, G-protein–coupled receptor; IP3, inositol 1,4,5-trisphosphate; IP3R, IP3 receptor; PIP2, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C.