Nerve Growth Factor Inhibits Apoptosis in Memory B Lymphocytes via Inactivation of p38 MAPK, Prevention of Bcl-2 Phosphorylation, and Cytochrome c Release

Maria Torcia, Giovanna De Chiara, Lucia Nencioni, Serena Ammendola, Danilo Labardi, Maria Lucibello, Paolo Rosini, Lionel N J L Marlier, Paolo Bonini, Persio Dello Sbarba, Anna Teresa Palamara, Nicola Zambrano, Tommaso Russo, Enrico Garaci, Federico Cozzolino

Research output: Contribution to journalArticle

Abstract

Survival of memory B lymphocytes is tightly linked to the integrity of the Bcl-2 protein and is regulated by a nerve growth factor (NGF) autocrine circuit. In factor-starved memory B cells, the addition of exogenous NGF promptly induced p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal kinase (JNK), dephosphorylation. Conversely, withdrawal of endogenous NGF was followed by p38 MAPK activation and translocation onto mitochondria, whereby it combined with and phosphorylated Bcl-2, as assessed by co-immunoprecipitation and kinase assays in vivo and in vitro. Mitochondria isolated from human memory B cells, then exposed to recombinant p38 MAPK, released cytochrome c, as did mitochondria from Bcl-2-negative MDCK cells loaded with recombinant Bcl-2. Apoptosis induced by NGF neutralization could be blocked by the specific p38 MAPK inhibitor SB203580 or by Bcl-2 mutations in Ser-87 or Thr-56. These data demonstrate that the molecular mechanisms underlying the survival factor function of NGF critically rely upon the continuous inactivation of p38 MAPK, a Bcl-2-modifying enzyme.

Original languageEnglish
Pages (from-to)39027-39036
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number42
DOIs
Publication statusPublished - Oct 19 2001

ASJC Scopus subject areas

  • Biochemistry

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    Torcia, M., De Chiara, G., Nencioni, L., Ammendola, S., Labardi, D., Lucibello, M., Rosini, P., Marlier, L. N. J. L., Bonini, P., Dello Sbarba, P., Palamara, A. T., Zambrano, N., Russo, T., Garaci, E., & Cozzolino, F. (2001). Nerve Growth Factor Inhibits Apoptosis in Memory B Lymphocytes via Inactivation of p38 MAPK, Prevention of Bcl-2 Phosphorylation, and Cytochrome c Release. Journal of Biological Chemistry, 276(42), 39027-39036. https://doi.org/10.1074/jbc.M102970200