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

Tom Joneson, Jennifer A. Fulton, Deanna J. Volle, Oleg V. Chaika, Dafna Bar-Sagi, Robert E Lewis

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Abstract

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 not 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.

Original languageEnglish (US)
Pages (from-to)7743-7748
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number13
DOIs
StatePublished - Mar 27 1998

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Mitogen-Activated Protein Kinases
Intercellular Signaling Peptides and Proteins
Chemical activation
Ligands
Phosphotransferases
Alleles
Phenotype
KSR-1 protein kinase
Caenorhabditis elegans
Cell growth
Phorbol Esters
Fibroblasts
Growth and Development
Mitogens
Modulators
Drosophila
Molecular Biology
Insulin
Membranes

ASJC Scopus subject areas

  • Biochemistry

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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. / Joneson, Tom; Fulton, Jennifer A.; Volle, Deanna J.; Chaika, Oleg V.; Bar-Sagi, Dafna; Lewis, Robert E.

In: Journal of Biological Chemistry, Vol. 273, No. 13, 27.03.1998, p. 7743-7748.

Research output: Contribution to journalArticle

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