Involvement of protein kinase C-δ in CD28-triggered cytotoxicity mediated by a human leukaemic cell line YT

F. J. Kos, H. D. Bear

Research output: Contribution to journalArticle

Abstract

Ligation of CD28 molecules expressed on the surface of human leukaemic natural killer-like YT cells triggers intracellular signals leading to cytolysis of target cells expressing CD80 or CD86 molecules. Known intracellular events include tyrosine phosphorylation, activation of phosphatidylinositol 3-kinase, and protein kinase C (PKC). In this study, we report that PKC-δ isoenzyme activity is required for CD28-triggered cytotoxicity mediated by YT cells and we also demonstrate that one of the primary targets of bryostatin 1, a modulator of PKC activity, is PKC-δ. Treatment of YT cells with bryostatin 1 caused degradation of PKC-δ, but not other PKC isoenzymes, and completely blocked the cytolytic activity of YT cells. In addition, PKC-δ-specific antibody introduced into YT cells by electroporation inhibited partially the YT cell-mediated cytotoxicity of B- lymphoblastoid cell line JY. This effect was specific, since addition of anti-PKC-δ antibody-blocking peptide in combination with anti-PKC-δ antibody to YT cells for electropotation, neutralized the effect of this antibody. These results demonstrate that YT cell cytolytic activity is dependent on PKC-δ, which is selectively down-regulated by bryostatin 1.

Original languageEnglish (US)
Pages (from-to)575-579
Number of pages5
JournalImmunology
Volume94
Issue number4
DOIs
StatePublished - Aug 10 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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