The molecular scaffold KSR1 regulates the proliferative and oncogenic potential of cells

Robert L. Kortum, Robert E. Lewis

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

The specificity of signaling through mitogen-activated protein kinase pathways has been attributed to both the control of intensity and duration of signaling and the actions of protein scaffolds. Here we demonstrate that the molecular scaffold KSR1 regulates the intensity and duration of ERK activation to modulate a cell's proliferative and oncogenic potential. Deletion of KSR1 eliminates the prolonged phase of ERK activation induced by platelet-derived growth factor and blocks RasV12-induced transformation. The introduction of KSR1 into KSR1-/- mouse embryo fibroblasts causes a concentration-dependent increase in signaling and transformation, to a maximum at 14 times the wild-type KSR1 expression levels, but inhibits these responses at higher expression levels. An increase in KSR1 expression to levels that are optimal for signaling leads to a threefold increase in proliferative capacity and is coincident with the level of KSR1 expression that maximally associates with all members of the Raf/MEK/ERK cascade. These data reveal that cells contain a reserve proliferative capacity that is accessible by the optimal expression of a noncatalytic signaling component and that altering the expression level of a molecular scaffold can modulate the actions of growth factors and oncogenes.

Original languageEnglish (US)
Pages (from-to)4407-4416
Number of pages10
JournalMolecular and cellular biology
Volume24
Issue number10
DOIs
StatePublished - May 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The molecular scaffold KSR1 regulates the proliferative and oncogenic potential of cells'. Together they form a unique fingerprint.

Cite this