The dependence receptor hypothesis

Apoptosis. 2004 Jan;9(1):37-49. doi: 10.1023/B:APPT.0000012120.66221.b2.


A new family of functionally-related receptors has recently been proposed, dubbed dependence receptors. These proteins, only some of which share sequence similarities, display the common property that they transduce two different intracellular signals: in the presence of ligand, these receptors transduce a positive signal leading to survival, differentiation or migration; conversely, in the absence of ligand, the receptors initiate or amplify a signal for programmed cell death. Thus cells that express these proteins at sufficient concentrations manifest a state of dependence on their respective ligands. The signaling that mediates cell death induction upon ligand withdrawal is in large part uncharacterized, but typically includes a required interaction with, and cleavage by, specific caspases. Here, we review the current knowledge concerning dependence receptors, including the shared mechanisms for cell death induction and their potential relevance in nervous system development and regulation of tumorigenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Axons
  • Caspases / metabolism
  • Cell Movement
  • Enzyme Activation
  • Humans
  • Integrins / metabolism
  • Ligands
  • Models, Biological
  • Neoplasms / metabolism
  • Nerve Growth Factors / metabolism
  • Nervous System / metabolism
  • Netrin Receptors
  • Netrin-1
  • Receptor, Nerve Growth Factor
  • Receptors, Cell Surface / metabolism
  • Receptors, Nerve Growth Factor / metabolism
  • Signal Transduction
  • Tumor Suppressor Proteins


  • Integrins
  • Ligands
  • Nerve Growth Factors
  • Netrin Receptors
  • Receptor, Nerve Growth Factor
  • Receptors, Cell Surface
  • Receptors, Nerve Growth Factor
  • Tumor Suppressor Proteins
  • Netrin-1
  • Caspases