Inhibition of p70/p85 S6 kinase activities in T cells by dexamethasone. Academic Article uri icon

Overview

abstract

  • Glucocorticoids (GC) are potent immunosuppressive agents that interfere with interleukin-2 (IL-2)-dependent proliferation and IL-2 receptor signal transduction in T lymphocytes through complex mechanisms. Here we report that the basal activity, and IL-2- and phorbol ester-dependent activation of the p70/p85 S6 kinases (referred to collectively as pp70S6k) are inhibited by the glucocorticoid dexamethasone (Dex) in CTLL-20 cells. This Dex-induced inhibition is time- and dose-dependent, appears to be the consequence of pp70S6k dephosphorylation, and requires ongoing transcription. Attempts to establish a link between Dex action and those of known pp70S6k-regulating agents such as phosphatidylinositol 3-kinase, protein kinase A-stimulating agents, calyculin A-inhibited protein phosphatases, and rapamycin have been negative. Additional results with NIH3T3 cells suggest the existence of a T cell-specific blockade of pp70S6k by Dex. Implications are 2-fold: 1) pp70S6k inactivation may account for at least part of the immunosuppressive effects of GC in vivo, and 2) GC inactivation of pp70S6k is exerted through a novel, distinct mechanism that does not appear to be linked to any other known pp70S6k regulatory process.

publication date

  • September 1, 1996

Research

keywords

  • Dexamethasone
  • Protein Serine-Threonine Kinases
  • T-Lymphocytes

Identity

Scopus Document Identifier

  • 0029736949

Digital Object Identifier (DOI)

  • 10.1210/mend.10.9.8885245

PubMed ID

  • 8885245

Additional Document Info

volume

  • 10

issue

  • 9