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14-3-3 is involved in p75 neurotrophin receptor-mediated signal transduction.

The low affinity neurotrophin receptor (p75NTR) has been shown to mediate the apoptosis signaling to neural cells. However, the specific mechanisms of intracellular signal transduction of this process are largely unknown. To understand p75NTR-mediated signal transduction, we previously identified a protein that interacts with the intracellular domain of p75NTR, and we named it p75NTR-associated cell death executor (NADE). To elucidate further the signaling mechanisms utilized by p75NTR and NADE, we screened for NADE-binding protein(s) with the yeast two-hybrid method, and we identified 14-3-3epsilon as a NADE-binding protein in vivo. To examine whether 14-3-3epsilon affects the induction of p75NTR-mediated apoptosis, wild type or various deletion mutant forms of 14-3-3epsilon were co-expressed in HEK293, PC12nnr5, and oligodendrocytes. Interestingly, transient expression of the mutant form of 14-3-3epsilon lacking the 208-255 amino acid region blocked nerve growth factor-dependent p75NTR/NADE-mediated apoptosis, although this mutant form of 14-3-3epsilon continued to associate with NADE. These results suggest that 14-3-3epsilon plays an important role in the modulation of nerve growth factor-dependent p75NTR/NADE-mediated apoptosis.

Pubmed ID: 11278287

Authors

  • Kimura MT
  • Irie S
  • Shoji-Hoshino S
  • Mukai J
  • Nadano D
  • Oshimura M
  • Sato TA

Journal

The Journal of biological chemistry

Publication Data

May 18, 2001

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM55147

Mesh Terms

  • 14-3-3 Proteins
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Binding Sites
  • Cell Line
  • Embryo, Mammalian
  • Gene Library
  • Humans
  • Kinetics
  • Mice
  • Nerve Growth Factor
  • Oligodendroglia
  • PC12 Cells
  • Proteins
  • Rats
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Recombinant Proteins
  • Signal Transduction
  • Transfection
  • Tyrosine 3-Monooxygenase