Activation of natural killer cells via the Fc gamma RIII (CD16) requires initial tyrosine phosphorylation.
Triggering of the Fc gamma RIII (CD16) on natural killer (NK) cells by monoclonal antibodies or antibody-coated target cells stimulates a rapid phospholipase C (PLC)-mediated hydrolysis of inositol phospholipids and results in subsequent delivery of the lytic hit. The role of initial tyrosine phosphorylation in these events was investigated with a tyrosine protein kinase (TPK) inhibitor, genistein. At doses that inhibited CD16-triggered tyrosine phosphorylation of substrates in intact cells, genistein did not influence serine/threonine phosphorylation or target cell binding but prevented PLC activation, cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. These findings indicate that tyrosine phosphorylation is an early and critical event during receptor-mediated activation of the lytic machinery.
Ståhls
A
A
Department of Pathology, University of Helsinki, Finland.
Heiskala
M
M
Mustelin
T
T
Andersson
L C
LC
D000920:Antibody-Dependent Cell Cytotoxicity; D000943:Antigens, Differentiation / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D019833:Genistein; D007295:Inositol Phosphates / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000943:Antigens, Differentiation; D007295:Inositol Phosphates; D007529:Isoflavones; D011961:Receptors, Fc; D017452:Receptors, IgG; D019000:Phosphotyrosine; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases