Fcγ receptor activation induces the tyrosine phosphorylation of both phospholipase C (PLC)-γ1 and PLC-γ2 in natural killer cells

Adrian T. Ting, Larry M. Karnitz, Renee A. Schoon, Robert T. Abraham, Paul J. Leibson

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

Crosslinking of the low affinity immunoglobulin G (IgG) Fc receptor (FcγR type III) on natural killer (NK) cells initiates antibody-dependent cellular cytotoxicity. During this process, FcyR 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 FcyR 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-γ1 and/or PLC-γ2 are expressed in NK cells, and whether the PLC-γ isoforms are tyrosine phosphorylated in response to FcγR stimulation. Immunoblotting analyses with PLC-γ1- and PLC-γ2-specific antisera demonstrate that both isoforms are expressed in human NK cells. Furthermore, FcγR crosslinking triggers the tyrosine phosphorylation of both PLC-γ1 and PLC-γ2 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 FcγR-induced tyrosine phosphorylation of PLC-γ1 and PLC-γ2, and the subsequent release of inositol phosphates. These results suggest that FcγR-initiated phosphoinositide turnover in human NK cells is regulated by the tyrosine phosphorylation of PLC-γ. More broadly, these observations demonstrate that nonreceptor PTK(s) activated by crosslinkage of a multisubunit receptor can phosphorylate both PLC-γ isoforms.

Original languageEnglish (US)
Pages (from-to)1751-1755
Number of pages5
JournalJournal of Experimental Medicine
Volume176
Issue number6
DOIs
StatePublished - Dec 1 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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