Journal article
Bcl-2 Regulates Nonapoptotic Signal Transduction: Inhibition of c-Jun N-terminal Kinase (JNK) Activation by IL-1β and Hydrogen Peroxide
Molecular genetics and metabolism, Vol.64(1), pp.19-24
05/1998
DOI: 10.1006/mgme.1998.2704
PMID: 9682214
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.
Details
- Title: Subtitle
- Bcl-2 Regulates Nonapoptotic Signal Transduction: Inhibition of c-Jun N-terminal Kinase (JNK) Activation by IL-1β and Hydrogen Peroxide
- Creators
- Larisse Lee - Cardiology Branch, National Institutes of Health, Bethesda, Maryland, 20892-1650Kaikobad Irani - Cardiology Division, Johns Hopkins Medical School, Baltimore, Maryland, 21205Toren Finkel - Cardiology Branch, National Institutes of Health, Bethesda, Maryland, 20892-1650
- Resource Type
- Journal article
- Publication Details
- Molecular genetics and metabolism, Vol.64(1), pp.19-24
- DOI
- 10.1006/mgme.1998.2704
- PMID
- 9682214
- NLM abbreviation
- Mol Genet Metab
- ISSN
- 1096-7192
- eISSN
- 1096-7206
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 05/1998
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984046829102771
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