Dependence of Both Spontaneous and Antibody-Dependent, Granule Exocytosis-Mediated NK Cell Cytotoxicity on Extracellular Signal-Regulated Kinases

摘要: Extracellular signal-regulated kinases (ERK, also known as mitogen-activated protein kinases) are serine-threonine transducing signals elicited upon ligand binding to several tyrosine kinase-associated receptors. We have reported that ERK2 phosphorylation and activation follows engagement of the low affinity receptor for Fc portion IgG (CD16) on NK cells, is necessary CD16-induced TNF-α mRNA expression. Here, we analyzed involvement ERK in cell-mediated cytotoxicity IFN-γ expression induced stimulation with targets coated or not Abs. Our data indicate that, immune complexes, occurs human primary cells interaction target sensitive granule exocytosis-mediated spontaneous cytotoxicity, this regulates both cell- complex-induced A specific inhibitor kinase reduced Ab-dependent a dose-dependent manner involving, at least part, inhibition exocytosis without affecting effector/target cell rearrangement cytoskeleton proteins actin tubulin. Involvement regulation Ca 2+ -dependent was confirmed, using genetic approach, infected recombinant vaccinia virus encoding an inactive mutant. These biochemical pathways receptors responsible either recognition although distinct, utilize one their downstream molecules regulate effector functions.