Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo.
While scaffold proteins are thought to be key components of signaling pathways, their exact function is unknown. By preassembling multiple components of signaling cascades, scaffolds are predicted to influence the efficiency and/or specificity of signaling events. Here we analyze a potential scaffold of the Ras/mitogen-activated protein kinase (MAPK) pathway, kinase suppressor of Ras (KSR), by generating KSR-deficient mice. KSR-deficient mice were grossly normal even though ERK kinase activation was attenuated to a degree sufficient to block T-cell activation and inhibit tumor development. Consistent with its role as a scaffold, high-molecular-weight complexes containing KSR, MEK, and ERK were lost in the absence of KSR. This demonstrates that KSR is a bona fide scaffold that is not required for but enhances signaling via the Ras/MAPK signaling pathway.
Nguyen
AnhCo
A
Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Burack
W Richard
WR
Stock
Jeffrey L
JL
Kortum
Robert
R
Chaika
Oleg V
OV
Afkarian
Maryam
M
Muller
William J
WJ
Murphy
Kenneth M
KM
Morrison
Deborah K
DK
Lewis
Robert E
RE
McNeish
John
J
Shaw
Andrey S
AS
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002455:Cell Division; D004789:Enzyme Activation; D005347:Fibroblasts; D005434:Flow Cytometry; D017353:Gene Deletion; D018390:Gene Targeting; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000032:analysis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008970:Molecular Weight; D010641:Phenotype; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases