Phosphatidylinositol-3 kinase activation induced upon Fc gamma RIIIA-ligand interaction.

Abstract

SummaryInduced activation of protein tyrosine kinase(s) is a central event in signal transduction mediated via the low affinity receptor for IgG (Fc3`RIIIA, 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 FcTRIII stimulation induces activation of phosphatidylinositol (PI)-3 kinase in NK cells. Phosphotyrosine immunoprecipitates from FcTRIII-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 ceUs expressing transfected Fc3'RIIIAol ligand binding chain in association with 3'2 or ('2 homodimers indicate that both complexes transduce this effect, although the FcTRIIIA-~'2 complexes do so with greater efficiency. Accumulation of phosphoinositide D3 phosphorylated products in stimulated ceUs confirms PI-3 kinase activation, indicating the participation of this enzyme in FcTRIIIA-mediated signal transduction.

Direct Tumor Lysis by NK Cells Uses a Ras-Independent Mitogen-Activated Protein Kinase Signal Pathway

“…Thus, Syk70 can potentially bypass Ras to activate MAPK. Because PI 3-kinase can be triggered by either CD94 or FcR cross-linking in NK cells (49,50), and Syk70 is critical for signaling NK activation (24 -26), it is possible that either of these molecules could control MAPK in NK cells during the lytic process.…”

Diversification of IgG effector functions

“…Likewise, FcγRIIIa-cross-linking on NK cells triggers cellular activation and the release of enzymes, such as perforin and granzymes, from intracellular granules that induces the formation of pores at the cell membrane of IgGcoated cellular targets, leading ultimately to the activation of pro-apoptotic pathways and cell death (22,74). Analogous cellular activation events are initiated upon FcγR cross-linking in other FcγR-expressing cell types, such as platelets.…”

Inhibition of the activating signals in NK92 cells by recombinant GST-sHLA-G1α chain

“…The protein-tyrosine kinases (PTKs) have been proved to provide early and requisite signals for cytotoxic function [18,19]. Since the phosphorylation of tyrosine can represent PTK activity, we next examined the effect of GST-sHLA-G1α chain on the tyrosine phosphorylation in NK92 cells induced by susceptible targets.…”