Untying the regulation of the Raf-1 kinase.
The Raf-1 kinase is the entry point to the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK-1/2) signaling pathway, which controls fundamental cellular functions including proliferation, differentiation, and survival. As such, Raf-1 is regulated by complex mechanisms that are incompletely understood. Recent results have shown that release from repression is an important event that facilitates the interaction of Raf-1 with the Ras activator and its substrate, MAPK/ERK-1/2 kinase. A number of distinct activation steps contribute in a combinatorial fashion to regulate and adjust Raf-1 activity. The efficiency of downstream signal transmission is modulated by protein:protein interactions, and new data consolidate an important role for kinase suppressor of ras (KSR) as a scaffolding protein. KSR is a dynamic scaffold whose function and localization is regulated by phosphorylation.
The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories Garscube Estate, Glasgow, UK.
Amardeep S
AS
Dhillon
Walter
W
Kolch
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D050356:Lipid Metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
D000242:Cyclic AMP; D019908:Proto-Oncogene Proteins c-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins