Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 34, Issue 18, Pages 3461-3472Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01633-13
Keywords
-
Categories
Funding
- NIH [R01 CA90040, R01 DK52809]
- American Diabetes Association
- NCI Minority Supplement through NIH [R01 CA90040]
- Skala Fellowship
- [T32 CA09476]
Ask authors/readers for more resources
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-Ras(V12)-induced replicative senescence, and H-Ras(V12)-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 factor-induced ERK activation at the early stages of pathway activation. Furthermore, abolishing the KSR1-caveolin-1 interaction increases growth factor demands to promote H-Ras(V12)-induced proliferation and has adverse effects on H-Ras(V12)-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available