Details

Autor(en) / Beteiligte

• Joneson, T
• Fulton, J A
• Volle, D J
• Chaika, O V
• Bar-Sagi, D
• Lewis, R E

Titel

Kinase Suppressor of Ras Inhibits the Activation of Extracellular Ligand-regulated (ERK) Mitogen-activated Protein (MAP) Kinase by Growth Factors, Activated Ras, and Ras Effectors

Ist Teil von

• The Journal of biological chemistry, 1998-03, Vol.273 (13), p.7743-7748

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• Kinase suppressor of Ras (KSR) is a loss-of-function allele that suppresses the rough eye phenotype of activated Ras in Drosophila and the multivulval phenotype of activated Ras in Caenorhabditis elegans . Genetic and biochemical studies suggest that KSR is a positive regulator of Ras signaling that functions between Ras and Raf or in a pathway parallel to Raf. We examined the effect of mammalian KSR expression on the activation of extracellular ligand-regulated (ERK) mitogen-activated protein (MAP) kinase in fibroblasts. Ectopic expression of KSR inhibited the activation of ERK MAP kinase by insulin, phorbol ester, or activated alleles of Ras, Raf, and mitogen and extracellular-regulated kinase. Expression of deletion mutants of KSR demonstrated that the KSR kinase domain was necessary and sufficient for the inhibitory effect of KSR on ERK MAP kinase activity. KSR inhibited cell transformation by activated Ras Val-12 but had no effect on the ability of Ras Val-12 to induce membrane ruffling. These data indicate that KSR is a potent modulator of a signaling pathway essential to normal and oncogenic cell growth and development.