Competitive signaling between TrkA and p75 nerve growth factor receptors determines cell survival

Sung Ok Yoon, Patrizia Casaccia-Bonnefil, Bruce Carter, Moses V. Chao

Research output: Contribution to journalArticlepeer-review

421 Scopus citations

Abstract

In addition to its role as a survival factor, nerve growth factor (NGF) has been implicated in initiating apoptosis in restricted cell types both during development and after terminal cell differentiation. NGF binds to the TrkA tyrosine kinase and the p75 neurotrophin receptor, a member of the tumor necrosis factor cytokine family. To understand the mechanisms underlying survival versus death decisions, the TrkA receptor was introduced into oligodendrocyte cell cultures that undergo apoptosis in a p75-dependent manner. Here we report that activation of the TrkA NGF receptor in oligodendrocytes negates cell death by the p75 receptor. TrkA-mediated rescue from apoptosis correlated with mitogen-activated protein kinase activation. Concurrently, activation of TrkA in oligodendrocytes resulted in suppression of c-jun kinase activity initiated by p75, whereas induction of NFκB activity by p75 was unaffected. These results indicate that TrkA-mediated rescue involves not only activation of survival signals but also simultaneous suppression of a death signal by p75. The selective interplay between tyrosine kinase and cytokine receptors provides a novel mechanism that achieves alternative cellular responses by merging signals from different ligand-receptor systems.

Original languageEnglish
Pages (from-to)3273-3281
Number of pages9
JournalJournal of Neuroscience
Volume18
Issue number9
DOIs
StatePublished - 1 May 1998
Externally publishedYes

Keywords

  • Apoptosis
  • Nerve growth factor
  • Neurotrophins
  • Oligodendrocyte
  • Protein kinase
  • Receptor crosstalk

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