Human T lymphocyte activation by tumor promoters: Role of protein kinase C

N. Isakov, A. Altman

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Protein kinase C (PKC) has a major role in a ligand-receptor-mediated signal transduction system in a variety of cell types including T lymphocytes. One of the early phenotypic changes associated with T cell activation is the expression of cell surface receptors for interleukin 2 (IL 2). To test the role of PKC in regulation of IL 2 receptor (IL 2-R) expression and T cell activation in general, we used tumor promoters (TP) as modulators of PKC and compared their effects on intact human T cells and on the enzymatic activity of T cell-derived PKC in a cellfree system. In T cells, the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced IL 2-R expression and proliferation associated with cytosol-to-membrane PKC translocation. A dose of TPA (1 to 4 ng/ml) that induced about 50% of the maximal activation of PKC in the enzymatic assay also induced half-maximal effects on cell proliferation, IL 2-R expression, and PKC redistribution in intact T cells. Structure-function studies with several phorbol ester analogs and non-phorbol ester TP directly correlated tumor promotion activity with the ability to activate PKC and indue IL 2-R. An inhibitor of PKC, chlorpromazine, was found to suppress TPA-mediated proliferation and IL 2-R expression, and inhibited T cell-derived PKC by competing with the phospholipid. Ca2+ ionophore, which synergizes with TPA in induction of T cell proliferation, facilitated the TPA-induced PKC translocation to the membrane. The results thus demonstrate a direct correlation between the effects of various chemicals on: a) subcellular redistribution of PKC in T cells; b) induction of T cell proliferation and IL 2-R expression; and c) activation of T cell-derived PKC in vitro. These data provide further supports for the role of PKC in transduction of activation signals in T cells and in regulation of IL 2-R expression.

Original languageEnglish
Pages (from-to)3100-3107
Number of pages8
JournalJournal of Immunology
Volume138
Issue number10
StatePublished - 1 Jan 1987
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Human T lymphocyte activation by tumor promoters: Role of protein kinase C'. Together they form a unique fingerprint.

Cite this