Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase Academic Article uri icon

Overview

MeSH Major

  • Interleukin-2
  • Polyenes
  • Protein Kinases
  • Receptors, Interleukin-2
  • T-Lymphocytes

abstract

  • The macrolide rapamycin induces cell cycle G1 arrest in yeast and in mammalian cells, which suggests that an evolutionarily conserved, rapamycin-sensitive pathway may regulate entry into S phase. In mammals, rapamycin inhibits interleukin-2 receptor-induced S phase entry and subsequent T-cell proliferation, resulting in immunosuppression. Here we show that interleukin-2 selectively stimulates the phosphorylation and activation of p70 S6 kinase but not the erk-encoded MAP kinases and rsk-encoded S6 kinases. Rapamycin completely and rapidly inhibits interleukin-2-induced phosphorylation and activation of p70 S6 kinase at concentrations comparable to those blocking S phase entry of T cells (0.05-0.2 nM). The structurally related macrolide FK506 competitively antagonizes the actions of rapamycin, indicating that these effects are mediated by FKBP, which binds the transition-state mimic structure common to both rapamycin and FK506 (refs 4, 6, 9-11). The selective blockade of the p70 S6 kinase activation cascade by the rapamycin-FKBP complex implicates this signalling pathway in the regulation of T cell entry into S phase.

publication date

  • July 2, 1992

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 1614535

Additional Document Info

start page

  • 70

end page

  • 3

volume

  • 358

number

  • 6381