title: KSR stimulates Raf-1 activity in a kinase-independent manner.
abstract: 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.
authors.affiliation: Molecular Basis of Carcinogenesis Laboratory, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Michaud
authors.forename: M
authors.initials: M
authors.lastname: Therrien
authors.forename: A
authors.initials: A
authors.lastname: Cacace
authors.forename: L C
authors.initials: LC
authors.lastname: Edsall
authors.forename: S
authors.initials: S
authors.lastname: Spiegel
authors.forename: G M
authors.initials: GM
authors.lastname: Rubin
authors.forename: D K
authors.initials: DK
authors.lastname: Morrison
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002518:Ceramides / Q000494:pharmacology; D004789:Enzyme Activation; D011494:Protein Kinases / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*
chemical_list: D002518:Ceramides; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D019908:Proto-Oncogene Proteins c-raf