FcγRI activation of phospholipase Cγ1 and protein kinase C in dibutyryl cAMP‐differentiated U937 cells is dependent solely on the tyrosine‐kinase activated form of phosphatidylinositol‐3‐kinase

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Abstract
The human high affinity receptor for immunoglobulin G, FcγRI, in dibutyryl cyclic AMP (dbcAMP)-differentiated U937 cells, is coupled to the activation of phospholipase C (PLC) and the conventional protein kinase C (PKC) isoforms, α, β, and γ. Here we demonstrate that aggregation of FcγRI activates the tyrosine-kinase regulated form of phosphatidylinositol-3-kinase (PI-3-kinase) and that an increase of phosphatidylinositol trisphosphate (PIP3) is essential for the activation and translocation of PLCγ1 in these cells. In addition, activation of the PKC isoforms was ablated by specific inhibitors of PI3-kinase or by overexpression of a dominant negative p85 subunit of PI3-kinase. The findings reported here demonstrate that PLCγ1 and PKC activation by FcγRI are downstream of PI3-kinase, and that in contrast to cytokine primed cells, only the tyrosine-kinase activated isoform of PI3-kinase is coupled to FcγRI in dbcAMP-differentiated cells.