R-Ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of the Ras effector pathways.
Curr Biol
; 7(1): 63-70, 1997 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-8999998
ABSTRACT
BACKGROUND:
The small GTPase R-Ras displays a less potent transforming activity than the closely related Ras oncogene products. Although R-Ras has been reported to interact with c-Raf1 and Ral-GDS in vitro, the pathways by which it exerts its effects on cellular proliferation are not known.RESULTS:
Both Ras and R-Ras interact with phosphoinositide (PI) 3-kinase in vitro, and induce elevation of the levels of PI 3-kinase lipid products in intact cells. Unlike Ras, R-Ras does not activate Raf or mitogen-activated protein (MAP) kinase in cells. In co-transfection assays, the serine/threonine protein kinase PKB (or Akt) is effectively stimulated by R-Ras, Ras, mutants of Ras that activate PI 3-kinase but not other effectors, and activated forms of PI 3-kinase. Ras and R-Ras stimulate PKB/Akt through a non-autocrine mechanism that involves PI 3-kinase. The constitutive activation of PI 3-kinase alone is sufficient to activate PKB/Akt, but not the MAP kinase ERK or the stress-activated protein kinase, Jun N-terminal kinase. Transformation assays in fibroblasts suggest that PKB/Akt and Raf are part of distinct oncogenic signalling pathways.CONCLUSIONS:
Both the Raf-MAP kinase and PI 3-kinase-PKB/Akt pathways are activated by Ras, but only the PI 3-kinase-PKB/Akt pathway is activated by R-Ras. PI 3-kinase, and downstream targets such as PKB/Akt, are likely to be essential mediators of transformation induced by R-Ras. PI 3-kinase, as well as Raf, is thus implicated also in Ras transformation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfotransferases (Aceptor do Grupo Álcool)
/
Proteínas Quinases Dependentes de Cálcio-Calmodulina
/
Proteínas ras
/
GTP Fosfo-Hidrolases
Limite:
Animals
Idioma:
En
Revista:
Curr Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Reino Unido