Regulation of ras signaling dynamics by Sos-mediated positive feedback.
Curr Biol
; 16(21): 2173-9, 2006 Nov 07.
Article
em En
| MEDLINE
| ID: mdl-17084704
ABSTRACT
The RTK-Ras-ERK cascade is a central signaling module implicated in the control of diverse biological processes including cell proliferation, differentiation, and survival. The coupling of RTK to Ras is mediated by the Ras-specific nucleotide-exchange factor Son of Sevenless (Sos), which activates Ras by inducing the exchange of GDP for GTP . Considerable evidence indicates that the duration and amplitude of Ras signals are important determinants in controlling the biological outcome . However, the mechanisms that regulate the quantitative output of Ras signaling remain poorly understood. We define a previously unrecognized regulatory component of the machinery that specifies the kinetic properties of signals propagated through the RTK-Ras-ERK cascade. We demonstrate that the establishment of a positive feedback loop involving Ras.GTP and Sos leads to an increase in the amplitude and duration of Ras activation in response to EGF stimulation. This effect is propagated to downstream elements of the pathway as reflected by sustained EGF-induced ERK phosphorylation and enhanced SRE-dependent transcription. As a consequence, the physiological endpoint of EGF action is switched from proliferation to differentiation. We propose that the engagement of Ras/Sos positive feedback loop may contribute to the mechanism by which ligand stimulation is coupled to discrete biological responses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas ras
/
Proteínas Son Of Sevenless
/
Retroalimentação Fisiológica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos