Stimulation of the phosphatidyl-inositol pathway can induce T-cell activation

Dev M. Desai, Marianne E. Newton, Theresa Kadlecek, Arthur Weiss

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

THE T-cell antigen receptor (TCR) regulates two signal transduction pathways: the phosphatidylinositol (Ptdlns)1 and tyrosine kinase pathways2. Stimulation of T cells with antigen or anti-TCR monoclonal antibodies induces an increase in inositol phosphates and diacylglycerol1,3 the second messengers responsible for the mobilization of cytoplasmic free calcium and activation of protein kinase C4. The TCR also activates a tyrosine kinase that is not intrinsic to the TCR2. The relationship between these two signal transduction pathways and their contribution to later T-cell responses is unclear. Studies using variants of a murine hybridoma suggested that the Ptdlns pathway might not be necessary for or be involved in regulating interleukin-2 (IL-2) production5. To address the relationship between later T-cell responses and the early biochemical signals, we investigated the ability of a heterologous receptor with defined signal transduction function to induce T-cell activation. The human muscarinic subtype-1 receptor (HMI)6, which elicits Ptdlns metabolism in neuronal cells through a G protein-coupled mechanism7, also functionally activates this pathway when expressed in the T-cell line Jurkat-derived host, J-HM1-2.2 (ref. 8). We show here that stimulation of HM1 alone induced IL-2 production and IL-2 receptor a chain expression. HM1 does not induce the tyrosine kinase pathway, suggesting that this pathway does not directly influence later T cell-activation responses. Instead, our studies indicate that activation of the Ptdlns pathway is probably sufficient to induce later T-cell responses.

Original languageEnglish (US)
Pages (from-to)66-69
Number of pages4
JournalNature
Volume348
Issue number6296
DOIs
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • General

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