SERINE THREONINE PHOSPHORYLATION OF THE GAMMA-SUBUNIT AFTER ACTIVATION OF THE HIGH-AFFINITY FC RECEPTOR FOR IMMUNOGLOBULIN-G

In this report we show that interferon gamma treatment of U937 cells induces increased expression of the gamma-subunit of the high-affinity Fc receptor for IgG (Fc gamma RI). Interferon treatment results in a 10-fold increased expression of the gamma-subunit and induces expression of a phosphorylated form (gamma(1)). The increased expression of the gamma-subunit correlates with its ability to transmit a signal via Fc gamma R, as measured by activation of the respiratory burst using insoluble immune complexes. During Fc gamma R activation, a mobility shift occurs in the phosphorylated form of this gamma(1)-subunit. Phosphoamino acid analysis demonstrates that this gamma(1) subunit is threonine phosphorylated in resting differentiated U937 cells and becomes predominantly serine phosphorylated on Fc receptor activation. The mobility shift in the gamma-subunit can be induced by treating U937 cells with phorbol 12-myristate 13-acetate or by monoclonal antibody cross-linking of Fc gamma RI. Hence the gamma-subunit is serine phosphorylated in response to Fc gamma RI and protein kinase C activation. Therefore the gamma-subunit, initially described as a subunit of Fc epsilon RI, now appears to be involved in signal transduction via Fc gamma RI. The data also suggest that the gamma-subunit, in contrast with the zeta-subunit of the T-cell receptor-CD3 complex, is a substrate for serine/threonine kinase(s) in the cell. The serine phosphorylation of the gamma-subunit suggests a divergence of structure and function between the gamma-subunit and its homologue, the zeta-subunit of the T-cell receptor. Phosphorylation of the gamma-subunit on serine may play some regulatory role in Fc gamma RI signal transduction in myeloid cells.