Protein-protein interactions in the regulation of the extracellular signal-regulated kinase.
The extracellular signal-regulated kinase (ERK) cascade is a central intracellular signaling pathway that is activated by a variety of extracellular stimuli, and thereby regulates cellular processes such as proliferation, differentiation, and oncogenic transformation. To execute these functions, the signals of those stimuli are transmitted to the cytosolic and nuclear targets in a rapid and specific manner. In the last few years it has become clear that the specificity and the rapid function of the ERK cascade is largely determined by protein-protein interactions with various signaling components and substrates. This review describes interactions of ERK with its immediate regulators, scaffold proteins, substrates, and localizing proteins, and shows their involvement in the functioning of the ERK cascade. Understanding the full scope of ERK-interactions is important for the development of new drugs for the treatment of cancer and other diseases.
Chuderland
Dana
D
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Seger
Rony
R
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases