KSR stimulates Raf-1 activity in a kinase-independent manner

NR Michaud, M Therrien, A Cacace… - Proceedings of the …, 1997 - National Acad Sciences
NR Michaud, M Therrien, A Cacace, LC Edsall, S Spiegel, GM Rubin, DK Morrison
Proceedings of the National Academy of Sciences, 1997National Acad Sciences
Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras-
dependent signaling pathways. Here, we find that murine KSR (mKSR1) translocates from
the cytoplasm to the plasma membrane in the presence of activated Ras. At the membrane,
mKSR1 modulates Ras signaling by enhancing Raf-1 activity in a kinase-independent
manner. The activation of Raf-1 is mediated by the mKSR1 cysteine-rich CA3 domain and
involves a detergent labile cofactor that is not ceramide. These findings reveal another point …
Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras-dependent signaling pathways. Here, we find that murine KSR (mKSR1) translocates from the cytoplasm to the plasma membrane in the presence of activated Ras. At the membrane, mKSR1 modulates Ras signaling by enhancing Raf-1 activity in a kinase-independent manner. The activation of Raf-1 is mediated by the mKSR1 cysteine-rich CA3 domain and involves a detergent labile cofactor that is not ceramide. These findings reveal another point of regulation for Ras-mediated signal transduction and further define a noncatalytic role for mKSR1 in the multistep process of Raf-1 activation.
National Acad Sciences