Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo

Anh Co Nguyen, W. Richard Burack, Jeffrey L. Stock, Robert Kortum, Oleg V. Chaika, Maryam Afkarian, William J. Muller, Kenneth M. Murphy, Deborah K. Morrison, Robert E. Lewis, John McNeish, Andrey S. Shaw

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210 Scopus citations

Abstract

While scaffold proteins are thought to be key components of signaling pathways, their exact function is unknown. By preassembling multiple components of signaling cascades, scaffolds are predicted to influence the efficiency and/or specificity of signaling events. Here we analyze a potential scaffold of the Ras/mitogenactivated protein kinase (MAPK) pathway, kinase suppressor of Ras (KSR), by generating KSR-deficient mice. KSR-deficient mice were grossly normal even though ERK kinase activation was attenuated to a degree sufficient to block T-cell activation and inhibit tumor development. Consistent with its role as a scaffold, high-molecular-weight complexes containing KSR, MEK, and ERK were lost in the absence of KSR. This demonstrates that KSR is a bona fide scaffold that is not required for but enhances signaling via the Ras/MAPK signaling pathway.

Original languageEnglish (US)
Pages (from-to)3035-3045
Number of pages11
JournalMolecular and cellular biology
Volume22
Issue number9
DOIs
Publication statusPublished - May 6 2002

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Nguyen, A. C., Burack, W. R., Stock, J. L., Kortum, R., Chaika, O. V., Afkarian, M., ... Shaw, A. S. (2002). Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo. Molecular and cellular biology, 22(9), 3035-3045. https://doi.org/10.1128/MCB.22.9.3035-3045.2002