Cavin-3 dictates the balance between ERK and Akt signaling.
Elife
; 2: e00905, 2013 Sep 24.
Article
em En
| MEDLINE
| ID: mdl-24069528
ABSTRACT
Cavin-3 is a tumor suppressor protein of unknown function. Using both in vivo and in vitro approaches, we show that cavin-3 dictates the balance between ERK and Akt signaling. Loss of cavin-3 increases Akt signaling at the expense of ERK, while gain of cavin-3 increases ERK signaling at the expense Akt. Cavin-3 facilitates signal transduction to ERK by anchoring caveolae to the membrane skeleton of the plasma membrane via myosin-1c. Caveolae are lipid raft specializations that contain an ERK activation module and loss of the cavin-3 linkage reduces the abundance of caveolae, thereby separating this ERK activation module from signaling receptors. Loss of cavin-3 promotes Akt signaling through suppression of EGR1 and PTEN. The in vitro consequences of the loss of cavin-3 include induction of Warburg metabolism (aerobic glycolysis), accelerated cell proliferation, and resistance to apoptosis. The in vivo consequences of cavin-3 knockout are increased lactate production and cachexia. DOIhttp//dx.doi.org/10.7554/eLife.00905.001.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
MAP Quinases Reguladas por Sinal Extracelular
/
Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas Proto-Oncogênicas c-akt
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article