Caveolin-1 is required for kinase suppressor of Ras 1 (KSR1)-mediated extracellular signal-regulated kinase 1/2 activation, H-RasV12-induced Senescence, and transformation

Robert L. Kortum, Mario R. Fernandez, Diane L. Costanzo-Garvey, Heidi J. Johnson, Kurt W. Fisher, Deanna J. Volle, Robert E. Lewis

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates the activation of the Raf/MEK/extracellular signal-regulated kinase (ERK) signal transduction pathway. KSR1 disruption in mouse embryo fibroblasts (MEFs) abrogates growth factor-induced ERK activation, H-RasV12-induced replicative senescence, and H-RasV12-induced transformation. Caveolin-1 has been primarily described as a major component of the coating structure of caveolae, which can serve as a lipid binding adaptor protein and coordinates the assembly of Ras, Raf, MEK, and ERK. In this study, we show that KSR1 interacts with caveolin-1 and is responsible for MEK and ERK redistribution to caveolin-1-rich fractions. The interaction between KSR1 and caveolin-1 is essential for optimal activation of ERK as a KSR1 mutant unable to interact with caveolin-1 does not efficiently mediate growth factorinduced ERK activation at the early stages of pathway activation. Furthermore, abolishing the KSR1-caveolin-1 interaction increases growth factor demands to promote H-RasV12-induced proliferation and has adverse effects on H-RasV12-induced cellular senescence and transformation. These data show that caveolin-1 is necessary for optimal KSR1-dependent ERK activation by growth factors and oncogenic Ras.

Original languageEnglish (US)
Pages (from-to)3461-3472
Number of pages12
JournalMolecular and cellular biology
Issue number18
StatePublished - 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Caveolin-1 is required for kinase suppressor of Ras 1 (KSR1)-mediated extracellular signal-regulated kinase 1/2 activation, H-Ras<sup>V12</sup>-induced Senescence, and transformation'. Together they form a unique fingerprint.

Cite this