Murine Ksr interacts with MEK and inhibits Ras-induced transformation

@article{DenouelGaly1998MurineKI,
  title={Murine Ksr interacts with MEK and inhibits Ras-induced transformation},
  author={Anne Denouel-Galy and Elizabeth M. J. Douville and P. H. Warne and Catherine Papin and Danielle Laugier and Georges Calothy and Julian Downward and Alain Eych{\`e}ne},
  journal={Current Biology},
  year={1998},
  volume={8},
  pages={46-55}
}
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Epidermal Growth Factor Treatment Enhances the Kinase Activity of Kinase Suppressor of Ras*

A two-stage in vitro kinase assay is established in which KSR never comes in contact with any recombinant kinases other than c-Raf-1, showing that KSR immunoprecipitated from quiescent COS-7 cells overexpressing Flag-tagged KSR was inactive, but its activity was rapidly and markedly induced upon epidermal growth factor treatment.

KSR: a MAPK scaffold of the Ras pathway?

The model now emerging is that KSR acts as a scaffolding protein that coordinates the assembly of a membrane-localized, multiprotein MAP kinase complex, a vital step in Ras-mediated signal transduction, and while Kinase Suppressor of Ras may be its name, phosphorylation may not be its game.

Kinase Suppressor of Ras Forms a Multiprotein Signaling Complex and Modulates MEK Localization

It is shown here that two predicted kinase-dead mutants of KSR retain the ability to complement ksr-1 loss-of-function alleles in C. elegans, suggesting that KSR may have physiological, kin enzyme-independent functions.

Deficiency of kinase suppressor of Ras1 prevents oncogenic ras signaling in mice.

KSR1 may represent a therapeutic target for Ras/MAPK signaling of human tumorigenesis and genetic support for the notion that epidermal growth factor receptor, Ras, and KSR1 are on the same signaling pathway in mammals is provided.

The Kinase Activity of Kinase Suppressor of Ras1 (KSR1) Is Independent of Bound MEK*

The results of this in vitro reconstitution assay support the contention that the kinase activity of KSR1 is an intrinsic property of this protein independent of K SR1-bound endogenous MEK.

KSR and CNK: two scaffolds regulating RAS-mediated RAF activation

The possibility that KSR, a RAF-like protein, does not solely act as a scaffold, but directly induces RAF catalytic function by a kinase-independent mechanism apparently shared by RAF- like proteins is discussed.

KSR is a scaffold required for activation of the ERK/MAPK module.

It is suggested that KSR functions as a scaffold that assembles the RAF/MEK functional pair, and that these interactions lead to the formation of a RAF/ MEK complex, thereby positioning RAF in close proximity to its substrate MEK.

Identification of B-KSR1, a Novel Brain-Specific Isoform of KSR1 That Functions in Neuronal Signaling

Findings demonstrate the functional importance of MEK binding and indicate that B-KSR1 may function to transduce Ras-dependent signals that are required for neuronal differentiation or that are involved in the normal functioning of the mature central nervous system.

Proteomic characterization of the dynamic KSR-2 interactome, a signaling scaffold complex in MAPK pathway.

KSR-1 Binds to G-protein βγ Subunits and Inhibits βγ-induced Mitogen-activated Protein Kinase Activation*

It is demonstrated that KSR-1 translocation to the plasma membrane is mediated, at least in part, by an interaction with βγ and that this interaction may modulate mitogen-activated protein kinase signaling.
...

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