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Fosforilación del sustrato mTOR en el control del crecimiento

Stefania Battaglioni¹, Don Benjamin¹, Matthias Wälchli¹

¹Biozentrum, University of Basel, Spitalstrasse 41, 4056 Basel, Switzerland.

|May 17, 2022

Resumen

El objetivo de la rapamicina (TOR) quinasa regula el crecimiento celular y el metabolismo. Los complejos TOR de mamíferos mTORC1 y mTORC2 fosforilan sustratos distintos utilizando un motivo común, a pesar de compartir una subunidad catalítica.

Área de la Ciencia:

Biología molecular
El metabolismo celular
La bioquímica

Sus antecedentes:

El objetivo de la rapamicina (TOR) es una serina / treonina quinasa crucial que regula el crecimiento celular y el metabolismo.
La señalización TOR es activada por nutrientes, factores de crecimiento y niveles de energía celular.
TOR existe en dos complejos distintos, TORC1 y TORC2, con diferentes funciones.

Objetivo del estudio:

Examinar e identificar todos los sustratos directos de TOR de mamíferos (mTOR).
Para aclarar cómo mTORC1 y mTORC2 fosforilan sustratos distintos.
Comprender el mecanismo de reclutamiento de sustratos por los complejos mTOR basado en datos estructurales.

Principales métodos:

Revisión exhaustiva de la literatura sobre la señalización mTOR.
Identificación de los sustratos mTOR directos.
Análisis de la información estructural relativa a los complejos mTOR.

Principales resultados:

Se han identificado numerosos sustratos directos para mTOR.
Se ha demostrado que mTORC1 y mTORC2 fosforilan conjuntos distintos de sustratos.
Se demostró que ambos complejos utilizan un motivo de fosforilación común.

Conclusiones:

mTORC1 y mTORC2, a pesar de una subunidad catalítica compartida, exhiben especificidad de sustrato.
Los dos complejos reclutan diferentes sustratos a través de mecanismos distintos.
Un motivo mínimo común es fosforilado por ambos complejos mTOR, lo que indica una regulación coordinada.

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