IL-2 deprivation triggers apoptosis which is mediated by c-Jun N-terminal kinase 1 activation and prevented by Bcl-2

Cell Death Differ. 1999 Jan;6(1):87-94. doi: 10.1038/sj.cdd.4400458.

Abstract

A variety of environmental stresses, as well as inflammatory cytokines, induce activation of c-Jun N-terminal kinases. We describe here that IL-2 deprivation-induced apoptosis in TS1alphabeta cells does not modify c-Jun protein levels and correlates Bcl-2 downregulation and an increase in JNK1, but not JNK2, activity directly related to the induction of apoptosis. Indeed, downregulation of JNK1 expression using antisense oligonucleotides inhibits apoptosis induced by IL-2 withdrawal. Overexpression of Bcl-2 promotes cell survival and blocks JNK1 activation as well as apoptosis caused by IL-2 deprivation. This suggests that inhibition of the JNK1 signaling pathway may be a mechanism through which Bcl-2 promotes cell survival and prevents apoptosis triggered by growth factor withdrawal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Down-Regulation
  • Enzyme Activation
  • Flow Cytometry
  • Gene Expression Regulation
  • Interleukin-2 / deficiency*
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases*
  • Oligonucleotides, Antisense / pharmacology
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Signal Transduction
  • T-Lymphocytes / metabolism*

Substances

  • Interleukin-2
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases