Bcl-2 regulates nonapoptotic signal transduction: Inhibition of c-Jun N- terminal kinase (JNK) activation by IL-1β and hydrogen peroxide

Larisse Lee, Kaikobad Irani, Toren Finkel

Research output: Contribution to journalArticle

Abstract

We have explored the role of bcl-2 as a potential modulator of intracellular signal transduction. Stable expression of bcl-2 in fibroblasts inhibited the activation of the c-jun amino terminal kinase (JNK) by the nonapoptotic cytokine interleukin-1β (IL-1β). This effect appeared to be selective for JNK activation as bcl-2 did not appear to alter other aspects of IL-1β signal transduction. Similarly, bcl-2 did not inhibit all activators of JNK as it had no effect on JNK activation by the protein synthesis inhibitor anisomycin. Treatment with nonlethal concentrations of H2O2, which resulted in the simultaneous stimulation of mitogen-activated protein kinase (MAPK) and JNK, demonstrated that bcl-2 appeared to alter the balance of activation of these two kinase cascades. The pathway by which bcl- 2 inhibits JNK activation is demonstrated to be independent of the rac1 GTPase. In contrast, the reduction in JNK activity in cells expressing bcl-2 can be restored by costimulation with a calcium ionophore. This suggests that bcl-2 can regulate certain nonapoptotic signaling pathways. Such results therefore expand the functions of bcl-2 and may have important implication in the understanding of the role of this protein in a variety of human diseases.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalMolecular Genetics and Metabolism
Volume64
Issue number1
DOIs
StatePublished - May 1998
Externally publishedYes

Keywords

  • Bcl-2
  • Calcium
  • JNK
  • Rac1

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

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