Phosphatidylinositol 3-kinase links the interleukin-2 receptor to protein kinase B and p70 S6 kinase

J Biol Chem. 1997 May 30;272(22):14426-33. doi: 10.1074/jbc.272.22.14426.

Abstract

Phosphatidylinositol 3-kinase (PI 3-kinase) is activated by the cytokine interleukin-2 (IL-2). We have used a constitutively active PI 3-kinase to identify IL-2-mediated signal transduction pathways directly regulated by PI 3-kinase in lymphoid cells. The serine/threonine protein kinase B (PKB)/Akt can act as a powerful oncogene in T cells, but its positioning in normal T cell responses has not been explored. Herein, we demonstrate that PKB is activated by IL-2 in a PI 3-kinase-dependent fashion. Importantly, PI 3-kinase signals are sufficient for PKB activation in IL-2-dependent T cells, and PKB is a target for PI 3-kinase signals in IL-2 activation pathways. The present study establishes also that PI 3-kinase signals or PKB signals are sufficient for activation of p70 S6 kinase in T cells. PI 3-kinase can contribute to, but is not sufficient for, activation of extracellular signal-regulated kinases (Erks) and Erk effector pathways. Therefore, PI 3-kinase is a selective regulator of serine/threonine kinase signal transduction pathways in T lymphocytes, and this enzyme provides a crucial link between the interleukin-2 receptor, the protooncogene PKB, and p70 S6 kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Activation
  • Humans
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Receptors, Interleukin-2 / metabolism*
  • Ribosomal Protein S6 Kinases
  • Signal Transduction*
  • T-Lymphocytes / metabolism*
  • Tumor Cells, Cultured

Substances

  • Proto-Oncogene Proteins
  • Receptors, Interleukin-2
  • Phosphotransferases (Alcohol Group Acceptor)
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases