Cross-linking of Fc receptors for IgA, FcaR (CD89), on monocytes/macrophages is known to enhance phagocytic activity and generation of oxygen free radicals. We provide evidence here that the FcaR signals through the g subunit of FceRI in U937 cells differentiated with interferon g (IFNg). Our results provide the first evidence that FcaR-mediated signals modulate a multimolecular adaptor protein complex containing Grb2, Shc, SHIP, CrkL, Cbl, and SLP-76. Cross-linking of FcaRI using anti-FcaRI induces the phosphorylation of the g subunit as detected by mobility retardation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Stimulation of FcaRI induced the tyrosine phosphorylation of Shc and increased the association of Grb2 with Shc and CrkL. Grb2 associates constitutively with Sos, and the latter undergoes mobility shift upon FcaRI stimulation. The complex adapter proteins, Cbl and SLP-76, are physically associated in myeloid cells and both proteins undergo tyrosine phosphorylation upon FcaR stimulation. These data indicate that the stimulation of FcaR results in the modulation of adaptor complexes containing tyrosine-phosphorylated Cbl, Shc, SHIP, Grb2, and Crkl. Experiments performed with the Src kinase inhibitor, PP1, provide the first evidence that Src kinase activation is required for FcaRI-induced production of superoxide anions and provide insight into the mechanism for FcaR-mediated activation of downstream oxidant signaling in myeloid cells. r 1999 by The American Society of Hematology.