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La fosforilación y regulación de Akt/PKB por el complejo rictor-mTOR
D D Sarbassov1, David A Guertin, Siraj M Ali
1Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|February 19, 2005
Resumen
El objetivo del complejo de rapamicina (TOR), incluido el TOR de ríctor y mamífero (mTOR), es crucial para la fosforilación de Akt / proteína quinasa B (PKB) en Ser473. Este complejo puede ser un objetivo terapéutico en cánceres que carecen de PTEN.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La señalización celular de las células.
- Oncología Oncología.
Sus antecedentes:
- La desregulación de la vía Akt/proteína quinasa B (PKB) está relacionada con el cáncer y la diabetes.
- La activación de Akt/PKB requiere fosforilación en Thr308 por PDK1 y Ser473 por una quinasa desconocida.
Objetivo del estudio:
- Para identificar la quinasa responsable de la fosforilación de Ser473 por Akt/PKB.
- Para investigar el papel del objetivo del complejo de rapamicina (TOR) en la activación de Akt/PKB.
Principales métodos:
- Experimentos realizados en Drosophila y células humanas.
- Análisis de la expresión y función de la TOR (mTOR) de los rictores y los mamíferos.
- Ensayos de fosforilación in vitro de Akt/PKB por el complejo rictor-mTOR.
Principales resultados:
- Rictor y mTOR son esenciales para la fosforilación de Akt/PKB Ser473.
- La reducción de la expresión de rictor o mTOR inhibió la actividad del efector Akt/PKB.
- El complejo rictor-mTOR fosforila directamente Akt/PKB en Ser473 y facilita la fosforilación de Thr308 por PDK1.
Conclusiones:
- El complejo rictor-mTOR es la quinasa responsable de la fosforilación de Akt/PKB Ser473.
- El Rictor-mTOR actúa como un regulador crucial de la activación de Akt/PKB.
- Rictor-mTOR representa un objetivo terapéutico potencial en los tumores con deficiencia de PTEN.
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