KSR and CNK: two scaffolds regulating RAS-mediated RAF activation.
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.
Clapéron
A
A
Institute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal CP, Montréal, Québec, Canada.
Therrien
M
M
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002384:Catalysis; D029721:Drosophila Proteins / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D048490:raf Kinases / Q000378:metabolism*; D018631:ras Proteins / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C115753:CNK protein, Drosophila; C504803:CNK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D048490:raf Kinases; D018631:ras Proteins