SFKs in GPIb-IX-V proximal signaling. The SFKs Src and Lyn associate with the GPIbα subunit and initiate inside-out signaling. Binding of VWF to the extracellular region of GPIbα induces SFK activation and phosphorylation of downstream substrates, including the ITAM-containing FcR γ-chain (FcR γ) and FcγRIIA, both of which act as high-affinity docking sites for the tandem SH2 domain–containing protein-tyrosine kinase Syk. The FcR γ-chain is reported to associate with the GPIbα subunit. However, GPIb-IX-V can signal in an ITAM-independent manner. Fyn and PKCδ associate and reciprocally activate one another, propagating the signal.