American Society of Hematology

Figure 2.

Outside-in signaling downstream of SFKs and Syk. SFKs phosphorylate a host of enzymes and signaling adaptors downstream of activated αIIbβ3, which are important for processes such as platelet spreading. These include PLCγ2, FAK, and ADAP, which in turn further propagate signal transduction. PLCγ2 catalyzes the formation of DAG and IP3 from membrane PtdIns(4,5)P2, leading to PKC activation and calcium liberation, respectively. PKCβ and PKCθ can localize to the β3-integrin tail via RACK1. FAK activation can be supported by CIB-1 bound to the αIIb C-terminal tail, and FAK substrates include the actin-binding protein α-actinin. Syk kinase phosphorylates further downstream targets, including SLP-76, and Vav-family RhoGEFs, which interplay with SFK substrates to propagate outside-in signaling. Hashed lines represent phosphorylation events, denoted on proteins by a yellow circle. Syk may also associate directly with the β3-integrin C-terminal tail.

Outside-in signaling downstream of SFKs and Syk. SFKs phosphorylate a host of enzymes and signaling adaptors downstream of activated α_IIbβ₃, which are important for processes such as platelet spreading. These include PLCγ2, FAK, and ADAP, which in turn further propagate signal transduction. PLCγ2 catalyzes the formation of DAG and IP₃ from membrane PtdIns(4,5)P₂, leading to PKC activation and calcium liberation, respectively. PKCβ and PKCθ can localize to the β₃-integrin tail via RACK1. FAK activation can be supported by CIB-1 bound to the α_IIb C-terminal tail, and FAK substrates include the actin-binding protein α-actinin. Syk kinase phosphorylates further downstream targets, including SLP-76, and Vav-family RhoGEFs, which interplay with SFK substrates to propagate outside-in signaling. Hashed lines represent phosphorylation events, denoted on proteins by a yellow circle. Syk may also associate directly with the β₃-integrin C-terminal tail.

This Feature Is Available To Subscribers Only