Interaction between lck and syk family tyrosine kinases in Fcγ receptor- initiated activation of natural killer cells

A. T. Ting, C. J. Dick, R. A. Schoon, L. M. Karnitz, R. T. Abraham, P. J. Leibson

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Ligation of the FcγR on natural killer (NK) cells results in the tyrosine phosphorylation of multiple substrates critical for intracellular signaling and activation of NK cell effector functions. However, it remains unclear which nonreceptor protein-tyrosine kinases (PTK) participate in this process. In this report we demonstrate that FcγR ligation induced the tyrosine phosphorylation and increased the catalytic activities of both syk family PTKs, ZAP-70, and syk. The phosphorylation of ZAP-70 and syk was enhanced markedly by overexpression of wild-type lck but not by a kinase-inactive mutant, suggesting that early FcγR-initiated activation of lck results in the subsequent regulation of syk family PTKs. The regulatory interplay between src and syk family PTKs was emphasized further by the observation that lck overexpression enhanced the association of ZAP-70 with the ζ chain of the FcγR complex. Additional analyses indicated that lck induced the subsequent tyrosine phosphorylation of phospholipase C (PLC)-γ2. Interestingly, the regulatory effects of lck on ZAP-70, syk, and PLC-γ2 could not be replaced by overexpression of either fyn or src, demonstrating a selective role for lck in effectively coupling FcγR stimulation to critical downstream signaling events. Taken together, our results suggest not only that FcγR stimulation on NK cells is coupled to the intracellular activation of both ZAP-70 and syk, but that the src family member, lck, can selectively regulate this tyrosine kinase cascade.

Original languageEnglish (US)
Pages (from-to)16415-16421
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number27
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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