Stimulation of the phosphatidylinositol pathway can induce T-cell activation

Nature. 1990 Nov 1;348(6296):66-9. doi: 10.1038/348066a0.


The T-cell antigen receptor (TCR) regulates two signal transduction pathways: the phosphatidylinositol (PtdIns) and tyrosine kinase pathways. Stimulation of T cells with antigen or anti-TCR monoclonal antibodies induces an increase in inositol phosphates and diacylglycerol, the second messengers responsible for the mobilization of cytoplasmic free calcium and activation of protein kinase C-4. The TCR also activates a tyrosine kinase that is not intrinsic to the TCR. 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 PtdIns pathway might not be necessary for or be involved in regulating interleukin-2 (IL-2) production. 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 (HM1), which elicits PtdIns metabolism in neuronal cells through a G protein-coupled mechanism, 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 alpha 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 PtdIns pathway is probably sufficient to induce later T-cell responses.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbachol / pharmacology
  • Cell Line
  • Enzyme Activation
  • Humans
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation*
  • Mice
  • Phosphatidylinositols / metabolism*
  • Protein Kinase C / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, T-Cell / physiology*
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / physiology
  • Receptors, Muscarinic / physiology
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology


  • Interleukin-2
  • Phosphatidylinositols
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Receptors, Muscarinic
  • Carbachol
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate