Possible mechanism of ITAM phosphorylation of GPVI/Fc receptor γ-chain complex. Collagen binds to the GPVI/FcR γ-chain complex via the GPVI-specific sequence glycine-proline-hydroxyproline (GPO). Collagen is believed to induce activation through the cross-linking of 2 GPVI complexes. The cytosolic tail of the FcR γ-chain has a proline-rich domain that binds to the SH3 domains of Src kinases. Considerable experimental evidence supports a role for Lyn and Fyn in signaling by GPVI. The 2 Src kinases Lyn and Fyn have been shown to associate with the proline-rich domain of GPVI via their SH3 domains. It is proposed that cross-linking of GPVI brings the Src kinases to the ITAM in the FcR γ-chain, thereby enabling phosphorylation of the 2 conserved tyrosines to take place. The interaction of a second tyrosine kinase Syk with these domains initiates a signaling cascade that leads to tyrosine phosphorylation of a number of downstream proteins, including the adapters LAT and SLP-76, and PLCγ2.