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Activación de la vía de la levadura Hippo por un ensamblaje dependiente de la fosforilación de complejos de
Jeremy M Rock1, Daniel Lim, Lasse Stach
1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|April 13, 2013
Resumen
Los andamios de señalización celular guían las decisiones celulares. La red de salida mitótica (MEN) utiliza un proceso de dos pasos donde Cdc15 fosforila Nud1, lo que permite la activación de Dbf2-Mob1, un mecanismo clave en la regulación del ciclo celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las proteínas del andamio juegan un papel crítico en las vías de transducción de señales.
- La red de salida mitótica (MEN) en la levadura en ciernes regula la progresión del ciclo celular.
- La vía MEN está evolucionariamente conservada y es homóloga a la vía Hippo en los metazoos.
Objetivo del estudio:
- Para dilucidar el mecanismo de transmisión de señales dentro de la cascada de la MEN quinasa.
- Para investigar el papel de la proteína del andamio Nud1 en la activación de la vía MEN.
- Para entender cómo se activa el complejo de efector quinasa Dbf2-Mob1.
Principales métodos:
- Ensayos de fosforilación para detectar la actividad de la quinasa.
- Co-inmunoprecipitación para estudiar las interacciones de las proteínas.
- Análisis de la levadura en ciernes (Saccharomyces cerevisiae) como organismo modelo.
Principales resultados:
- La señalización a través de la cascada MEN implica un nuevo proceso de activación en dos pasos.
- La MEN quinasa Cdc15 fosforila el andamio Nud1.1.
- Nud1 fosforilado crea un sitio de unión para Dbf2-Mob1, lo que lleva a su activación por Cdc15.
Conclusiones:
- Los hallazgos revelan un mecanismo único para la señalización asistida por andamios en la vía MEN.
- Este proceso de fosforilación y acoplamiento en dos pasos es crucial para activar el complejo de la quinasa Dbf2-Mob1.
- Este mecanismo puede representar un principio general para la transmisión de señales en otras cascadas de quinasa.
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