KSR is a scaffold required for activation of the ERK/MAPK module.
Mechanisms that regulate signal propagation through the ERK/MAPK pathway are still poorly understood. Several proteins are suspected to play critical roles in this process. One of these is Kinase Suppressor of Ras (KSR), a component previously identified in RAS-dependent genetic screens in Drosophila and Caenorhabditis elegans. Here, we show that KSR functions upstream of MEK within the ERK/MAPK module. In agreement with this, we found that KSR facilitates the phosphorylation of MEK by RAF. We further show that KSR associates independently with RAF and MEK, and that these interactions lead to the formation of a RAF/MEK complex, thereby positioning RAF in close proximity to its substrate MEK. These findings suggest that KSR functions as a scaffold that assembles the RAF/MEK functional pair.
Roy
François
F
Clinical Research Institute of Montreal, Laboratory of Intracellular Signaling, Montreal, PQ Canada H2W 1R7.
Laberge
Gino
G
Douziech
Mélanie
M
Ferland-McCollough
David
D
Therrien
Marc
M
D000818:Animals; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology*; D046911:Macromolecular Substances; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D018631:ras Proteins / Q000502:physiology
D029721:Drosophila Proteins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D019908:Proto-Oncogene Proteins c-raf; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins