Dominant-negative caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains.
Nat Cell Biol
; 1(2): 98-105, 1999 Jun.
Article
in En
| MEDLINE
| ID: mdl-10559881
ABSTRACT
The plasma membrane pits known as caveolae have been implicated both in cholesterol homeostasis and in signal transduction. CavDGV and CavKSY, two dominant-negative amino-terminal truncation mutants of caveolin, the major structural protein of caveolae, significantly inhibited caveola-mediated SV40 infection, and were assayed for effects on Ras function. We find that CavDGV completely blocked Raf activation mediated by H-Ras, but not that mediated by K-Ras. Strikingly, the inhibitory effect of CavDGV on H-Ras signalling was completely reversed by replenishing cell membranes with cholesterol and was mimicked by cyclodextrin treatment, which depletes membrane cholesterol. These results provide a crucial link between the cholesterol-trafficking role of caveolin and its postulated role in signal transduction through cholesterol-rich surface domains. They also provide direct evidence that H-Ras and K-Ras, which are targeted to the plasma membrane by different carboxy-terminal anchors, operate in functionally distinct microdomains of the plasma membrane.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane
/
Cholesterol
/
Proto-Oncogene Proteins p21(ras)
/
Sequence Deletion
/
Caveolins
/
Membrane Lipids
/
Membrane Proteins
Limits:
Animals
Language:
En
Journal:
Nat Cell Biol
Year:
1999
Document type:
Article
Affiliation country:
Australia