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Negative receptor signalling

Ivan Dikic1, Silvia Giordano

  • 1Ludwig Institute for Cancer Research, Husargatan 3, SE-75 124 Uppsala, Sweden. Ivan.Dikic@biochem2.de

Current Opinion in Cell Biology
|March 22, 2003
PubMed

Insights

Negative receptor signalling, involving proteins like Cbl and Sprouty, modulates cell stimulation. Dysregulation of these crucial inhibitory signals can lead to human diseases.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Cell membrane receptors initiate intracellular signaling pathways controlling cell fate (proliferation, differentiation, apoptosis).
  • Activated receptors trigger negative signaling to dampen positive signals and regulate cell stimulation.
  • Negative receptor signaling is crucial for normal cellular function.

Purpose of the Study:

  • To elucidate the molecular components involved in negative signaling by receptor tyrosine kinases.
  • To understand the coordinated action of proteins in modulating cellular responses.

Main Methods:

  • Review of recent studies on negative receptor signaling pathways.
  • Identification of key molecular players including ubiquitin ligases, adaptor proteins, inhibitory molecules, kinases, and metabolites.

Main Results:

  • Negative signaling involves a coordinated network of Cbl (ubiquitin ligase), Grb2 and CIN85 (adaptor proteins), Sprouty (inhibitory molecule), and activated Cdc42-associated kinase.
  • Phosphoinositol metabolites also play a role in this inhibitory cascade.
  • These components collectively decrease signal amplitude and modulate cell stimulation.

Conclusions:

  • Negative receptor signaling is a complex, coordinated process essential for maintaining cellular homeostasis.
  • Disruption of these inhibitory pathways is linked to the pathogenesis of various human diseases.

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