A negative-feedback loop regulating ERK1/2 activation and mediated by RasGPR2 phosphorylation.
Biochem Biophys Res Commun
; 474(1): 193-198, 2016 05 20.
Article
en En
| MEDLINE
| ID: mdl-27107697
ABSTRACT
The dynamic regulation of ERK1 and -2 (ERK1/2) is required for precise signal transduction controlling cell proliferation, differentiation, and survival. However, the underlying mechanisms regulating the activation of ERK1/2 are not completely understood. In this study, we show that phosphorylation of RasGRP2, a guanine nucleotide exchange factor (GEF), inhibits its ability to activate the small GTPase Rap1 that ultimately leads to decreased activation of ERK1/2 in cells. ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition. These studies identify RasGRP2 as a novel substrate of ERK1/2 and define a negative-feedback loop that regulates the BRaf-MEK-ERK signaling cascade. This negative-feedback loop determines the amplitude and duration of active ERK1/2.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Enzimológica de la Expresión Génica
/
Proteína Quinasa 1 Activada por Mitógenos
/
Sistema de Señalización de MAP Quinasas
/
Factores de Intercambio de Guanina Nucleótido
/
Retroalimentación Fisiológica
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2016
Tipo del documento:
Article