PMID:2068107

Citation	Einspahr, KJ, Abraham, RT, Binstadt, BA, Uehara, Y and Leibson, PJ (1991) Tyrosine phosphorylation provides an early and requisite signal for the activation of natural killer cell cytotoxic function. Proc. Natl. Acad. Sci. U.S.A. 88:6279-83
Abstract	Natural killer (NK) cells are a unique subpopulation of lymphocytes with the capability to kill malignant cells via one of two alternative mechanisms: (i) Fc receptor-dependent cytotoxicity against antibody-coated targets or (ii) direct cell-mediated cytotoxicity. However, the molecular mechanisms that trigger and subsequently regulate NK cell cytotoxicity are incompletely understood. We have therefore investigated the role of protein tyrosine phosphorylation in the transmembrane signaling initiated after Fc receptor stimulation or direct tumor cell contact in clonal CD16+/CD3- human NK cells. We report that stimulation of the Fc receptor rapidly induced the tyrosine phosphorylation of a number of NK cell proteins. These effects occurred within 2 min, were maximal at 10 min, and declined toward baseline after 60 min. In addition, Fc receptor ligation increased the in vitro protein kinase activity of NK cell phosphotyrosyl proteins. We have also demonstrated that direct contact of NK cells with K562 tumor cells induced the rapid phosphorylation of distinct NK cell phosphotyrosyl proteins. Furthermore, the protein-tyrosine kinase inhibitor herbimycin A blocked NK cell cytotoxic function in a concentration-dependent manner. Our results suggest that protein tyrosine phosphorylation is an obligatory early proximal signal in activating the cytotoxic function of NK cells.
Links	PubMed PMC52066
Keywords	Antibiotics, Antineoplastic/pharmacology; Antigens, CD/analysis; Benzoquinones; Cell Line; Cells, Cultured; Clone Cells; Cytotoxicity, Immunologic/drug effects; Humans; Killer Cells, Natural/drug effects; Killer Cells, Natural/immunology; Lactams, Macrocyclic; Lymphocyte Activation; Phosphorylation; Protein-Tyrosine Kinases/metabolism; Quinones/pharmacology; Receptors, Fc/drug effects; Receptors, Fc/immunology; Signal Transduction; Tyrosine
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:FCG3A		GO:0042269: regulation of natural killer cell mediated cytotoxicity	ECO:0000314:		P		Fig. 2 shows the results of a direct assay to show that FcR activates during the process of cytotoxicity.	complete

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