STIMULATION OF FC-ALPHA RECEPTORS INDUCES TYROSINE PHOSPHORYLATION OFPHOSPHOLIPASE C-GAMMA-1, PHOSPHATIDYLINOSITOL PHOSPHATE HYDROLYSIS, AND CA2+ MOBILIZATION IN RAT AND HUMAN MESANGIAL CELLS

Although knowledge of IgA Fc receptor (Fc alpha R) structure and gene organization has progressed in the past few years, signal transduction pathways elicited by its activation have hardly been studied. Previou sly, we have demonstrated that mesangial cells (MC) possess Fc alpha R , and their stimulation triggers several biologic responses. In this w ork, we studied the early biochemical signals triggered by Fc alpha R stimulation in MC. MC incubation with aggregated IgA (AlgA) elicited a dose-dependent increase in cytosolic Ca2+ ([Ca2+](i)). The response w as rapid and transient, and slowly fell to the original baseline. Ca2 mobilization was dependent on the Fc region of the IgA, because Fc, b ut neither Fab fragment nor carbohydrates, inhibited the [Ca2+] rise. The initial induction of [Ca2+](i) rise was due to Ca2+ mobilization f rom inositol trisphosphate (IP3)-sensitive intracellular stores, while sustained levels were maintained through extracellular Ca2+ influx. S timulation of Fc alpha R also resulted in production of IP3, temporall y correlated with Ca2+ mobilization. Protein tyrosine kinase inhibitor s abolished [Ca2+](i) rise, indicating that tyrosine phosphorylation o f some substrates is required for Ca2+ mobilization. Stimulation throu gh Fc alpha R gave rise to a marked increase in tyrosine phosphorylati on of several proteins, including the 147-kDa band, similar in size to phospholipase C gamma 1 (PLC-gamma 1). Tyrosine phosphorylation of PL C-gamma 1 reached a maximum 30 s after stimulation, as determined by i mmunoprecipitation and Western blot. Collectively, these results indic ate that the Fc alpha R signaling pathway in MC involves PLC-gamma 1 a ctivation, IP3 formation, and Ca2+ mobilization, and is linked to acti vation of tyrosine kinases.