Negative receptor signalling

Curr Opin Cell Biol. 2003 Apr;15(2):128-35. doi: 10.1016/s0955-0674(03)00004-8.


Binding of external factors to cell membrane receptors triggers intracellular signalling pathways that ultimately determine if the cell proliferates, differentiates or undergoes apoptosis. Activated receptors also initiate a cascade of events, called negative receptor signalling, that decreases the amplitude of positive signals and modulates the level of cell stimulation. Recent studies have revealed that negative signalling by receptor tyrosine kinases involves coordinated action of ubiquitin ligases (i.e. Cbl), adaptor proteins (i.e. Grb2 and CIN85), inhibitory molecules (i.e. Sprouty), cytoplasmic kinases (i.e. activated Cdc42-associated kinase) and phosphoinositol metabolites. These inhibitory signals are essential for normal cell functioning, and their deregulation often results in human diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Down-Regulation / genetics*
  • Eukaryotic Cells / metabolism*
  • Feedback, Physiological / physiology*
  • Humans
  • Phosphatidylinositols / metabolism
  • Phosphotransferases / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction / physiology*
  • Ubiquitins / metabolism


  • Adaptor Proteins, Vesicular Transport
  • Phosphatidylinositols
  • Receptors, Cell Surface
  • Ubiquitins
  • Phosphotransferases