Stimulation of FcγRIIIA results in phospholipase C-γ1 tyrosine phosphorylation and p56lck activation

Abstract

Binding of ligand to the α subunit of FcγRIIIA(CD16), expressed at the natural killer (NK) cell membrane in association with homo or heterodimers of proteins of the ζ family, results in phosphorylation of several proteins on tyrosine residues. We have analyzed the role of protein tyrosine phosphorylation in the regulation of molecular events induced upon stimulation of FcγRIIIA in NK cells and in T cells expressing the FcγRIIIα chain in association with endogenous ζ2 homodimers and devoid of other (CD3, CD2) transducing molecules. Our data indicate that treatment of these cells with protein tyrosine kinase inhibitors prevents not only FcγRIIIA-induced protein tyrosine phosphorylation but also phosphatidylinositol 4,5 diphosphate hydrolysis and increased intracellular Ca2+ concentration, indicating a primary role of tyrosine kinase(s) in the induction of these early activation events. Occupancy of FcγRIIIA by ligand results in phospholipase C (PLC)-γ1 tyrosine phosphorylation in NK cells and in FcγRIIIA-transfected CD3-/CD2- T cells, and induces functional activation of p56lck in FcγRIIIAα/ζ2-transfected T cells, suggesting the possibility that the receptor-induced PLC-γ1 activation occurs upon phosphorylation of its tyrosine residues mediated by this kinase and is, at least in part, responsible for the signal transduction mediated via CD16 upon ligand binding.