Feedback regulation of Ras signaling by Rabex-5-mediated ubiquitination.
Curr Biol
; 20(15): 1372-7, 2010 Aug 10.
Article
em En
| MEDLINE
| ID: mdl-20655225
ABSTRACT
Ras proteins play a central role in transducing signals that control cell proliferation, differentiation, motility, and survival. The location-specific signaling activity of Ras has been previously shown to be regulated by ubiquitination [1]. However, the molecular machinery that controls Ras ubiquitination has not been defined. Here we demonstrate through biochemical and functional analyses that Rabex-5 (also known as RabGEF1) [2, 3] functions as an E3 ligase for Ras. Rabex-5-mediated Ras ubiquitination promotes Ras endosomal localization and leads to the suppression of ERK activation. Moreover, the Ras effector RIN1 [4, 5] is required for Rabex-5-dependent Ras ubiquitination, suggesting a feedback mechanism by which Ras activation can be coupled to ubiquitination. These findings define new elements in the regulatory circuitry that link Ras compartmentalization to signaling output.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endossomos
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Proteínas ras
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Fatores de Troca do Nucleotídeo Guanina
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Retroalimentação Fisiológica
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Ubiquitina-Proteína Ligases
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article