The monocyte Fc receptors FcRI/ and FcRIIA differ in their interaction with Syk- and Src-related tyrosine kinases

Abstract: There are important differences in sig-naling between the Fc receptor for immunoglobu-lin G (IgG; FcR) IIA, which uses the Ig tyrosine-activating motif (ITAM) within its own cytoplasmic domain, and FcRI, which transmits signals by means of an ITAM located within the cytoplasmic domain of its associated -chain. For example, in transfected epithelial cells and COS-1 cells, FcRIIA mediates phagocytosis of IgG-coated red blood cells more efficiently than does FcRI/, and enhancement of phagocytosis by Syk kinase is more pronounced for FcRI/ than for FcRIIA. In addition, structure/function studies indicate that the -chain ITAM and the FcRIIA ITAM have different requirements for mediating the phago-cytic signal. To study the differences between FcRIIA and FcRI/, we examined the interac-tion of FcRIIA and the FcRI/ chimera FcRI-- (extracellular domain–transmembrane–cyto-plasmic domain) with Syk kinase and with the Src-related tyrosine kinases (SRTKs) Hck and Lyn in transfected COS-1 cells. Our data indicate that FcRIIA interacts more readily with Syk than does FcRI-- and suggest that one consequence may be the greater phagocytic efficiency of FcRIIA compared with FcRI/. Furthermore, individual SRTKs affect the efficiency of phagocytosis differ-ently for FcRI-- and FcRIIA and also influ-ence the ability of these receptors to interact with Syk kinase. Taken together, the data suggest that differences in signaling by FcRIIA and FcRI-- are related in part to interaction with Syk and Src kinases and that individual SRTKs play different roles in FcR-mediated phagocytosis. J. Leukoc