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

Oncogene volume 26, pages 3143–3158 (2007)Cite this article

Abstract

The RAS-RAF-MEK-extracellular-regulated kinase (RAS/ERK) pathway is a major intracellular route used by metazoan cells to channel to downstream targets a diverse array of signals, including those controlling cell proliferation and survival. Recent findings suggest that the pathway is assembled by specific scaffolding proteins that in turn regulate the efficiency, the location and/or the duration of signal transmission. Here, through the angle of studies conducted in Drosophila and C. elegans, we present two such proteins, the kinase suppressor of RAS (KSR) and connector enhancer of KSR (CNK) scaffolds, and highlight their implication in a novel mechanism regulating RAS-mediated RAF activation. Based on recent findings, we discuss 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.

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Acknowledgements

We thank Dariel Ashton-Beaucage and Gino Laberge for helpful discussions and critical reading of the paper. AC is supported by a fellowship from La Fondation pour la Recherche Médicale (FRM; France) and MT is recipient of a Canadian Research Chair. This work was supported by grants from the Canadian Institutes of Health Research and the National Cancer Institute of Canada with funds from the Canadian Cancer Society.

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  1. Institute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal CP,, Montréal, Québec, Canada

    A Clapéron & M Therrien

  2. Département de pathologie et de biologie cellulaire, Université de Montréal, 6128 Succursale Centre-Ville, Montréal, Québec, Canada

    M Therrien

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  1. A Clapéron
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  2. M Therrien
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Correspondence to M Therrien.

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Clapéron, A., Therrien, M. KSR and CNK: two scaffolds regulating RAS-mediated RAF activation. Oncogene 26, 3143–3158 (2007). https://doi.org/10.1038/sj.onc.1210408

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