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Regulación de la vía Hippo-YAP por medio de la señalización de receptores acoplados a proteínas G
Fa-Xing Yu1, Bin Zhao, Nattapon Panupinthu
1Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
Cell
|August 7, 2012
Resumen
La señalización del receptor acoplado a la proteína G (GPCR) regula la vía de Hippo. Las señales extracelulares como LPA y S1P pueden inhibir o activar la señalización Hippo-YAP, impactando el crecimiento celular y la migración en el cáncer.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Oncología Oncología.
Sus antecedentes:
- La vía de Hippo es esencial para el control del tamaño del órgano y su desregulación está relacionada con el cáncer.
- Los reguladores aguas arriba de la vía del hipopótamo mamífero siguen siendo en gran medida desconocidos.
- Las quinasas del núcleo de la vía Hippo, Lats1/2, inhiben YAP y TAZ, coactivadores transcripcionales clave.
Objetivo del estudio:
- Para identificar las señales aguas arriba que regulan la vía de los hipopótamos mamíferos.
- Para investigar el papel de la señalización del receptor acoplado a la proteína G (GPCR) en la regulación de la vía de Hippo.
- Para aclarar cómo los GPCR modulan la actividad de YAP y TAZ.
Principales métodos:
- Investigó el efecto de ligandos específicos de GPCR (LPA, S1P, glucagón, epinefrina) en los componentes de la vía Hippo.
- Se utilizaron ensayos basados en células para monitorear la actividad de la quinasa de Lats1/2.2.
- Se evaluó el impacto en la actividad transcripcional YAP/TAZ y en los procesos celulares aguas abajo como la migración y la proliferación.
Principales resultados:
- La señalización GPCR regula directamente la vía del hipopótamo.
- El ácido lisofosfatídico (LPA) y el 1-fosfofato de esfingosina (S1P) señalan a través de los receptores acoplados a G12/13 para inhibir Lats1/2, activando YAP/TAZ.
- El glucagón y la epinefrina señalan a través de los receptores acoplados a Gs para activar Lats1/2, inhibiendo la función YAP.
- YAP / TAZ median la expresión génica inducida por LPA, la migración celular y la proliferación.
Conclusiones:
- La señalización GPCR actúa como un regulador crítico aguas arriba de la vía Hippo-YAP.
- La vía Hippo-YAP es una rama clave de señalización aguas abajo para los GPCR.
- Las señales extracelulares modulan la actividad de la vía de Hippo, ofreciendo objetivos terapéuticos potenciales en el cáncer.
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