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El coactivador dependiente de la señal CBP es un objetivo nuclear para pp90RSKK
T Nakajima1, A Fukamizu, J Takahashi
1Department of Cellular and Molecular Physiology Harvard Medical School Boston, Massachusetts 02115, USA.
Cell
|August 9, 1996
Resumen
Los factores de crecimiento activan la vía Ras, lo que lleva a la S6 quinasa pp90RSK a unirse al coactivador CBP. Esta interacción reprime los genes receptivos a la cAMP mientras permite la inducción de genes receptivos a la Ras.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La señalización celular de las células.
- Regulación genética Reglamento genético.
Sus antecedentes:
- Los factores de crecimiento utilizan vías de señalización como Ras para regular los procesos celulares.
- La vía del monofosfato de adenosina cíclica (cAMP) es crucial para varias respuestas celulares.
- El diálogo cruzado entre las vías de señalización puede conducir a resultados celulares complejos.
Objetivo del estudio:
- Para dilucidar el mecanismo por el cual la activación de la vía Ras influye en la señalización cAMP.
- Para investigar el papel de la S6 quinasa pp90RSK y el coactivador CBP en este diálogo cruzado.
- Para entender cómo esta interacción afecta a la transcripción de genes específicos.
Principales métodos:
- Activación de la vía Ras utilizando insulina o el factor de crecimiento nervioso (NGF).
- Análisis de las interacciones proteína-proteína utilizando co-inmunoprecipitación para detectar el complejo pp90RSK-CBP.
- Evaluación de la transcripción génica a través de ensayos de actividad de CREB (proteína de unión al elemento sensible al CAMP).
Principales resultados:
- La insulina o el NGF indujeron el reclutamiento de la S6 quinasa pp90RSK al coactivador CBP.
- El complejo pp90RSK-CBP se formó con alta estequiometría y persistió durante 6-8 horas.
- La unión de pp90RSK a la CBP reprimió la transcripción de los genes sensibles a la cAMP, pero fue esencial para la inducción de genes sensibles a la Ras.
Conclusiones:
- La activación de la vía Ras interfiere con la señalización cAMP a través del complejo pp90RSK-CBP.
- Este acoplamiento cruzado se produce a nivel de un coactivador dependiente de la señal.
- El estudio demuestra un nuevo mecanismo de integración de señales entre las vías Ras y cAMP.
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