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Activación de la vía ERK/MAPK por una isoforma de rap1GAP asociada con G alfa (i)
N Mochizuki1, Y Ohba, E Kiyokawa
1Department of Pathology, Research Institute, International Medical Center of Japan, Tokyo.
Nature
|September 7, 1999
Resumen
La subunidad alfa de la proteína G (i) activa la vía ERK/MAPK mediante el reclutamiento de rap1GAPII. Esto reduce el Rap1 ligado al GTP, activando así la vía mitogénica Ras-ERK/MAPK.
Área de la Ciencia:
- Las vías de señalización celular.
- Biología molecular La biología molecular.
- Receptores acoplados a proteínas G acoplados a proteínas G.
Sus antecedentes:
- La proteína G ((i) heterotrimérica es crucial para la señalización de los receptores de neuropéptidos y hormonas.
- Las subunidades de proteína (alfa y betagamma) activan la cascada ERK/MAPK.
- El constitutivo activo G ((alfa) i2 (gip2) transforma las células y activa ERK/MAPK a través de un mecanismo desconocido.
Objetivo del estudio:
- Aclarar el mecanismo por el cual las subunidades alfa de la proteína G (i) activan la cascada ERK/MAPK.
- Para identificar nuevos reguladores de la vía Ras-ERK/MAPK.
- Para investigar el papel de la proteína II de activación de la GTPasa Rap1 (rap1GAPII) en la señalización G.
Principales métodos:
- Co-inmunoprecipitación para evaluar la unión a las proteínas.
- Pruebas de translocación celular para monitorear la localización de proteínas.
- Los ensayos Rap1 ligados a GTP cuantifican la actividad de Rap1.
- Pruebas de activación de ERK/MAPK.
Principales resultados:
- rap1GAPII se une específicamente a las subunidades alfa de las proteínas G.
- La estimulación de los receptores m2-muscarínicos acoplados a G (i) provoca la translocación de rap1GAPII a la membrana.
- Esta translocación conduce a una disminución de los niveles de Rap1 ligados al GTP.
- La reducción del Rap1 ligado al GTP activa la vía ERK/MAPK.
Conclusiones:
- La subunidad alfa de G ((i) activa la vía mitogénica Ras-ERK/MAPK.
- Esta activación se produce a través del reclutamiento por la membrana de rap1GAPII, que reduce el Rap1 ligado al GTP.
- rap1GAPII actúa como un eslabón crucial entre las subunidades alfa G (i) y la vía Ras-ERK/MAPK.
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