Fc gamma RI activation of phospholipase C gamma 1 and protein kinase C in dibutyryl cAMP-differentiated U937 cells is dependent solely on the tyrosine-kinase activated form of phosphatidylinositol-3-kinase

The human high affinity receptor for immunoglobulin G, Fc gamma RI, in dibu tyryl cyclic AMP (dbcAMP)-differentiated U937 cells, is coupled to the acti vation of phospholipase C (PLC) and the conventional protein kinase C (PKC) isoforms, alpha, beta, and gamma. Here we demonstrate that aggregation of Fc gamma RI activates the tyrosine-kinase regulated form of phosphatidylino sitol-3-kinase (PI-3-kinase) and that an increase of phosphatidylinositol t risphosphate (PIP,) is essential for the activation and translocation of PL C gamma 1 in these cells. In addition, activation of the PKC isoforms was a blated by specific inhibitors of PI3-kinase or by overexpression of a domin ant negative p85 subunit of PI3-kinase. The findings reported here demonstr ate that PLC gamma 1 and PKC activation by Fc gamma RI are downstream of PI 3-kinase, and that in contrast to cytokine primed cells, only the tyrosine- kinase activated isoform of PI3-kinase is coupled to Fc gamma RI in dbcAMP- differentiated cells.