1. ¹Institute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal CP, Montréal, Québec, Canada
2. ²Département de pathologie et de biologie cellulaire, Université de Montréal, 6128 Succursale Centre-Ville, Montréal, Québec, Canada

Correspondence: Dr M Therrien, Institute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal CP, 6128 Succursale Centre-Ville, Montréal, Québec H3C 3J7, Canada. E-mail: marc.therrien@umontreal.ca

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.