Fig. 3

αIIbβ3 bidirectional signaling. The agonists, such as thrombin, ADP, epinephrine, 5-HT, TXA2, or collagen, bind to their receptors causing intracellular signaling events, which then lead talin to bind to β3 tail with the help of kindlin (A and B). Then, αIIbβ3 conformation changes from bent-closed to extended-open state. Thus, the affinity of αIIbβ3 to fibrinogen increases (C). This process is called inside-out signaling transduction (C). Once fibrinogen binds to αIIbβ3, signal transfers from outside to inside, named as outside-in signaling transduction, causing Gα13 to bind to E⁷³¹XE⁷³³ motif, and Src to bind to R⁷⁶⁰GT⁷⁶² motif, accompanied by phosphorylation of Y⁷⁴⁷ and Y⁷⁵⁹ in β3 tail, as well as phosphorylation of Y⁴¹⁶ in Src. At last, the platelet spreading, aggregation, and clot retraction develop (D). For representative purposes, β tail is outsized