Negative receptor signalling.
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.
Dikic
Ivan
I
Ludwig Institute for Cancer Research, Husargatan 3, SE-75 124 Uppsala, Sweden. Ivan.Dikic@biochem2.de
Giordano
Silvia
S
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation / Q000235:genetics*; D005057:Eukaryotic Cells / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D014452:Ubiquitins; D010770:Phosphotransferases