Nerve growth factor (NGF) down-regulates the Bcl-2 homology 3 (BH3) domain-only protein Bim and suppresses its proapoptotic activity by phosphorylation.

The Journal of biological chemistry ·Vol. 277 ·No. 51 ·2002-12-20 ·Pages 49511-6

Biswas SC, Greene LA

Abstract

Bim is a proapoptotic, BH3-domain-only member of the Bcl-2 family that plays a role in death of trophic factor-deprived sympathetic neurons as well as in other paradigms of apoptotic death. We report here that nerve growth factor (NGF) leads to both a slow down-regulation of Bim expression in neuronal PC12 cells and rapid Bim phosphorylation. Both effects appear to be mediated by the MEK/MAPK pathway. An assay for Bim-mediated death revealed that NGF-promoted phosphorylation suppresses the proapoptotic activity of Bim. The phosphorylation sites responsible for this effect in the extra long form of rBim were identified as Ser-109 and Thr-110. Thus, NGF protects neurons from the proapoptotic effects of Bim both by acute phosphorylation and the longer term repression of expression.

MeSH Terms

Animals Apoptosis Apoptosis Regulatory Proteins Bcl-2-Like Protein 11 Binding Sites Blotting, Western Carrier Proteins/biosynthesis Cell Survival DNA, Complementary/metabolism Down-Regulation MAP Kinase Signaling System Membrane Proteins Mitogen-Activated Protein Kinases/metabolism Mutagenesis, Site-Directed Nerve Growth Factor/metabolism Neurons/metabolism PC12 Cells Phosphorylation Plasmids/metabolism Protein Binding Protein Structure, Tertiary Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2/chemistry Rats Serine/chemistry Threonine/chemistry Time Factors Transfection

Chemicals

Apoptosis Regulatory Proteins Bcl-2-Like Protein 11 Bcl2l11 protein, rat Carrier Proteins DNA, Complementary Membrane Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Threonine Serine Nerve Growth Factor Mitogen-Activated Protein Kinases

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Biswas Subhas C

Department of Pathology and Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, 630 W 168th Street, New York, NY 10032, USA.

Greene Lloyd A

Article Info

Journal

The Journal of biological chemistry

Abbr.

J Biol Chem

ISSN

0021-9258

DOI

10.1074/jbc.M208086200

Published

2002-12-20

Epub

2002-00-17

Pages

49511-6

Language

English

Region

United States

NLM ID

2985121R

Subset

External Links

PubMed source DOI: 10.1074/jbc.M208086200 View journal details

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Nerve growth factor (NGF) down-regulates the Bcl-2 homology 3 (BH3) domain-only protein Bim and suppresses its proapoptotic activity by phosphorylation.

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