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.

Torcia, M., De Chiara, G., Nencioni, L., Ammendola, S., Labardi, D., Lucibello, M., et al. (2001). Nerve growth factor inhibits apoptosis in memory B lymphocytes via inactivation of p38 MAPK, prevention of Bcl-2 phosphorylation, and cytochrome c release. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 276(42), 39027-39036 [10.1074/jbc.M102970200].

Nerve growth factor inhibits apoptosis in memory B lymphocytes via inactivation of p38 MAPK, prevention of Bcl-2 phosphorylation, and cytochrome c release

Ammendola S.;GARACI, ENRICO;
2001-01-01

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - Microbiologia e Microbiologia Clinica
English
Con Impact Factor ISI
Bioassay; Cells; Enzymes; Mutagenesis; Nerve growth factor (NGF); Biochemistry; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; cytochrome c; Janus kinase; mitogen activated protein kinase; nerve growth factor; protein bcl 2; serine; synaptophysin; threonine; DNA fragment; enzyme inhibitor; imidazole derivative; mitogen activated protein kinase kinase; mitogen activated protein kinase kinase 4; mitogen activated protein kinase p38; pyridine derivative; recombinant protein; stress activated protein kinase; animal cell; apoptosis; article; autocrine effect; B lymphocyte; cell survival; controlled study; enzyme activation; enzyme inactivation; human; human cell; immunoprecipitation; in vitro study; in vivo study; memory cell; mitochondrion; molecular biology; nonhuman; priority journal; protein function; protein phosphorylation; protein secretion; animal; cell culture; cell nucleus; chemistry; cytosol; drug antagonism; fluorescence microscopy; immunological memory; metabolism; pathology; phosphorylation; physiology; protein binding; protein transport; rat; serodiagnosis; time; Animalia; Janus; Animals; Apoptosis; B-Lymphocytes; Cell Nucleus; Cells, Cultured; Cytochrome c Group; Cytosol; DNA Fragmentation; Enzyme Inhibitors; Humans; Imidazoles; Immunologic Memory; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Microscopy, Fluorescence; Mitochondria; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Nerve Growth Factor; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Precipitin Tests; Protein Binding; Protein Transport; Proto-Oncogene Proteins c-bcl-2; Pyridines; Rats; Recombinant Proteins; Serine; Threonine; Time Factors
Torcia, M., De Chiara, G., Nencioni, L., Ammendola, S., Labardi, D., Lucibello, M., et al. (2001). Nerve growth factor inhibits apoptosis in memory B lymphocytes via inactivation of p38 MAPK, prevention of Bcl-2 phosphorylation, and cytochrome c release. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 276(42), 39027-39036 [10.1074/jbc.M102970200].
Torcia, M; De Chiara, G; Nencioni, L; Ammendola, S; Labardi, D; Lucibello, M; Rosini, P; Marlier, Lnjl; Bonini, P; Dello Sbarba, P; Palamara, At; Zambrano, N; Russo, T; Garaci, E; Cozzolino, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/52011
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