The monocyte Fcγ receptors FcγRI/γ and FcγRIIA differ in their interaction with Syk and with Src-related tyrosine...

There are important differences in signaling between the Fc receptor for immunoglobulin G (IgG) FcγRIIA, which uses the Ig tyrosine-activating motif (ITAM) within its own cytoplasmic domain, and FcγRI, which transmits signals by means of an ITAM located within the cytoplasmic domain of its associated γ-chain. For example, in transfected epithelial cells and COS-1 cells, FcγRIIA mediates phagocytosis of IgG-coated red blood cells more efficiently than does FcγRI/γ, and enhancement of phagocytosis by Syk kinase is more pronounced for FcγRI/γ than for FcγRIIA. In addition, structure/function studies indicate that the γ-chain ITAM and the FcγRIIA ITAM have different requirements for mediating the phagocytic signal. To study the differences between FcγRIIA and FcγRI/γ, we examined the interaction of FcγRIIA and the FcγRI/γ chimera FcγRI-γ-γ (extracellular domain-transmembrane domain-cytoplasmic domain) with Syk kinase and with the Src-related tyrosine kinases (SRTKs) Hck and Lyn in transfected COS-1 cells. Our data indicate that FcγRIIA interacts more readily with Syk than does FcγRI-γ-γ and suggest that one consequence may be the greater phagocytic efficiency of FcγRIIA compared with FcγRI/γ. Furthermore, individual SRTKs affect the efficiency of phagocytosis differently for FcγRI-γ-γ and FcγRIIA and also influence the ability of these receptors to interact with Syk kinase. Taken together, the data suggest that differences in signaling by FcγRIIA and FcγRI-γ-γ are related in part to interaction with Syk and Src kinases and that individual SRTKs play different roles in FcγR-mediated phagocytosis.