The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PIP3

Immunol Rev. 2003 Apr;192:7-20. doi: 10.1034/j.1600-065x.2003.00008.x.

Abstract

Ligation of the T cell receptor for antigen (TCR) and/or costimulatory receptor CD28 results in rapid activation of phosphoinositide-3 kinase (PI-3 kinase). It remains unclear, however, precisely how this activation occurs and also how the newly generated phospholipid products trigger the various events associated with T cell activation. Here we discuss the current understanding of how PI-3 kinase is activated by the TCR and CD28 and what roles its products play in T cell activation. We also review recent advances in understanding the function of Akt in particular, especially its role in CD28 costimulation. Several functional targets of Akt are discussed in this regard: inducible transcription, cell survival, glucose metabolism, and the cellular translational machinery. These pathways have been associated with TCR/CD28 costimulation, and they have also been implicated as targets of Akt.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • CD28 Antigens / physiology
  • Cell Cycle Proteins / metabolism*
  • Glucose / metabolism
  • Humans
  • Lymphocyte Activation
  • Models, Immunological
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins*
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*
  • Transcription Factors / metabolism

Substances

  • CD28 Antigens
  • Cell Cycle Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • Transcription Factors
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Glucose