NGF withdrawal induces apoptosis in CESS B cell line through p38 MAPK activation and Bcl-2 phosphorylation

Biochem Biophys Res Commun. 2000 Nov 30;278(3):753-9. doi: 10.1006/bbrc.2000.3871.

Abstract

The sIgG(+) lymphoblastoid B cell line CESS spontaneously produces a high amount of NGF and expresses both high affinity (p140(Trk-A)) and low affinity (p75(NTR)) NGF receptors. Blocking NGF signals with neutralizing antibodies or specific Trk-A inhibitors induces a rapid phosphorylation of antiapoptotic Bcl-2 protein, followed by caspase activation, and apoptotic death of CESS cells. Bcl-2 phosphorylation in several sites within a approximately 60 aa "loop" domain of protein is known to regulate its antiapoptotic function. Accordingly, CESS cells expressing the loop deletional mutant cDNA constructs Bcl-2 Delta40-91 were completely resistant to apoptosis induced by NGF withdrawal, indicating that Bcl-2 phosphorylation is a critical event. NGF withdrawal induces p38 MAPK, but not JNK, activation in CESS cells, and SB203580, a specific inhibitor of p38 MAPK, is able to prevent both Bcl-2 phosphorylation and apoptosis, indicating that p38 MAPK is the enzyme responsible for these events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • B-Lymphocytes
  • Carbazoles / pharmacology
  • Cell Division / drug effects
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Genes, bcl-2
  • Humans
  • Indole Alkaloids
  • JNK Mitogen-Activated Protein Kinases
  • Kinetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nerve Growth Factor / pharmacology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptor, trkA / genetics
  • Receptor, trkA / physiology
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / physiology
  • Sequence Deletion
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tumor Cells, Cultured
  • Tyrphostins / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • AG-879
  • Carbazoles
  • Enzyme Inhibitors
  • Indole Alkaloids
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Nerve Growth Factor
  • Tyrphostins
  • Nerve Growth Factor
  • staurosporine aglycone
  • Receptor, trkA
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases