Neurotrophin signaling via Trks and p75

Exp Cell Res. 1999 Nov 25;253(1):131-42. doi: 10.1006/excr.1999.4705.

Abstract

This review focuses on recent advances in our understanding of receptor-mediated signaling by the neurotrophins NGF, BDNF, NT3, and NT4/5. Two distinct receptor types have been distinguished, Trks and p75. The Trks are receptor tyrosine kinases that utilize a complex set of substrates and adapter proteins to activate defined secondary signaling cascades required for neurotrophin-promoted neuronal differentiation, plasticity, and survival. A specialized aspect of Trk/neurotrophin action in neurons is the requirement for retrograde signaling from the distal periphery to the cell body. p75 is a universal receptor for neurotrophins that is a member of the TNF receptor/Fas/CD40 superfamily. p75 appears to modify Trk signaling when the two receptor types are coexpressed. When expressed in the absence of Trks, p75 mediates responses to neurotrophins including promotion of apoptotic death. The mechanisms of p75 receptor signaling remain to be fully understood.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Nerve Growth Factors / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Type II
  • Signal Transduction*

Substances

  • Antigens, CD
  • Nerve Growth Factors
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • Receptor Protein-Tyrosine Kinases