Phosphatidylinositol-3 kinase activation induced upon FrγRIIIA-ligand interaction

Abstract

Induced activation of protein tyrosine kinase(s) is a central event in signal transduction mediated via the low affinity receptor for IgG (FcγRIIIA, CD16) in natural killer (NK) cells. Tyrosine phosphorylation may affect the function of several proteins directly, or indirectly by inducing their association with other tyrosine phosphorylated proteins. Here, we report that FcγRIII stimulation induces activation of phosphatidylinositol (PI)-3 kinase in NK cells. Phosphotyrosine immunoprecipitates from FcγRIII-stimulated NK cells contain PI-kinase activity and PI-3 kinase can be directly precipitated from them. Conversely, a series of tyrosine-phosphorylated proteins is coprecipitated with PI-3 kinase from the stimulated, but not from control cells. Analogous results obtained using Jurkat T cells expressing transfected FcγRIIIAα ligand binding chain in association with γ2 or ζ2 homodimers indicate that both complexes transduce this effect, although the FcγRIIIA-ζ2 complexes do so with greater efficiency. Accumulation of phosphoinositide D3 phosphorylated products in stimulated cells confirms PI-3 kinase activation, indicating the participation of this enzyme in FcγRIIIA-mediated signal transduction.