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Beta-arrestina 2: un andamio MAPK regulado por el receptor para la activación de JNK3
P H McDonald1, C W Chow, W E Miller
1Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Box 3821, Durham, NC 27710, USA.
Science (New York, N.Y.)
|November 25, 2000
Resumen
La beta-arrestina 2 actúa como una proteína de andamio, uniéndose a la c-Jun amino-terminal quinasa 3 (JNK3) y sus activadores. Esta interacción controla la actividad y la localización de JNK3 en respuesta a la estimulación del receptor acoplado a proteínas G (GPCR).
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La señalización celular de las células.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las beta-arrestinas son reguladores clave de la desensibilización, la internalización y la señalización del receptor acoplado a proteínas G (GPCR).
- Las funciones específicas de la beta-arrestina 2 en las vías de señalización intracelular más allá de la regulación de la GPCR no están completamente aclaradas.
Objetivo del estudio:
- Para identificar nuevos socios de unión de la beta-arrestina 2.
- Investigar el papel de la beta-arrestina 2 en la regulación de las vías de la proteína quinasa activada por mitógeno (MAPK), específicamente la c-Jun amino-terminal quinasa 3 (JNK3).
Principales métodos:
- Cribado de dos híbridos de levadura para identificar las interacciones proteína-proteína.
- Los ensayos de coinmunoprecipitación utilizan extractos de cerebro de ratón y células transfectadas COS-7.
- Transfección celular y estimulación del receptor de angiotensina II tipo 1A.
Principales resultados:
- La beta-arrestina 2 fue identificada como un socio de unión de JNK3, así como de los activadores de JNK3, la kinasa reguladora de la señal de apoptosis 1 (ASK1) y la kinasa MAPK 4.
- La expresión de beta-arrestina 2 condujo a la retención citosólica y a una mayor fosforilación estimulada por ASK1 de JNK3.
- La activación del receptor de angiotensina II tipo 1A dio lugar a la activación de JNK3 y a la colocalización de la betaarrestina 2 con JNK3 activo en las vesículas intracelulares.
Conclusiones:
- La beta-arrestina 2 funciona como una proteína de andamio, integrando la señalización GPCR con la vía JNK3 MAPK.
- La betaarrestina 2 modula la distribución espacial y la actividad del módulo de señalización JNK3 en respuesta a la estimulación GPCR.
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