Fc gamma receptor activation induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells

• Published in: The Journal of experimental medicine Vol. 176; no. 6; pp. 1751 - 1755
• Main Authors: Ting, A T, Karnitz, L M, Schoon, R A, Abraham, R T, Leibson, P J
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01.12.1992
• Subjects: Antibody-Dependent Cell Cytotoxicity; Benzoquinones; Cell Line; Enzyme Activation; Humans; Immunoblotting; Isoenzymes - metabolism; Killer Cells, Natural - drug effects; Killer Cells, Natural - enzymology; Killer Cells, Natural - immunology; Kinetics; Lactams, Macrocyclic; Phosphorylation; Phosphotyrosine; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Quinones - pharmacology; Receptors, IgG - metabolism; Rifabutin - analogs & derivatives; Type C Phospholipases - metabolism; Tyrosine - analogs & derivatives; Tyrosine - analysis
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.176.6.1751

Crosslinking of the low affinity immunoglobulin G (IgG) Fc receptor (Fc gamma R type III) on natural killer (NK) cells initiates antibody-dependent cellular cytotoxicity. During this process, Fc gamma R stimulation results in the rapid activation of phospholipase C (PLC), which hydrolyzes membrane phosphoinositides, generating inositol-1,4,5-trisphosphate and sn-1,2-diacylglycerol as second messengers. We have recently reported that PLC activation after Fc gamma R stimulation can be inhibited by a protein tyrosine kinase (PTK) inhibitor. Based on the paradigm provided by the receptor tyrosine kinases, we investigated whether PLC-gamma 1 and/or PLC-gamma 2 are expressed in NK cells, and whether the PLC-gamma isoforms are tyrosine phosphorylated in response to Fc gamma R stimulation. Immunoblotting analyses with PLC-gamma 1- and PLC-gamma 2-specific antisera demonstrate that both isoforms are expressed in human NK cells. Furthermore, Fc gamma R crosslinking triggers the tyrosine phosphorylation of both PLC-gamma 1 and PLC-gamma 2 in these cells. Phosphorylation of both isoforms is detectable within 1 min, and returns to basal level within 30 min. Pretreatment with herbimycin A, a PTK inhibitor, blocked the Fc gamma R-induced tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2, and the subsequent release of inositol phosphates. These results suggest that Fc gamma R-initiated phosphoinositide turnover in human NK cells is regulated by the tyrosine phosphorylation of PLC-gamma. More broadly, these observations demonstrate that nonreceptor PTK(s) activated by crosslinkage of a multisubunit receptor can phosphorylate both PLC-gamma isoforms.