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Published on: January 22, 2019
La rapamicina inhibe selectivamente la activación de la interleucina-2 de la kinasa p70 S6 de manera selectiva
C J Kuo1, J Chung, D F Fiorentino
1Howard Hughes Medical Institute, Unit in Molecular and Genetic Medicine, Beckman Center, Stanford University School of Medicine, California 94305-5425.
Nature
|July 2, 1992
Resumen
El macrolido rapamicina detiene la progresión del ciclo celular al inhibir la activación de la quinasa p70 S6. Este descubrimiento revela una vía conservada que regula la proliferación de células T y la inmunosupresión.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La rapamicina, un macrolido, detiene el ciclo celular en levaduras y células de mamíferos, lo que sugiere una vía reguladora conservada para la entrada en la fase S.
- En los mamíferos, la rapamicina inhibe la proliferación de células T al bloquear la entrada de la fase S inducida por el receptor de la interleucina-2, lo que lleva a la inmunosupresión.
Objetivo del estudio:
- Investigar el mecanismo por el cual la rapamicina inhibe la proliferación de células T inducida por la interleucina-2.
- Para identificar la vía de señalización específica dirigida por la rapamicina en las células T.
Principales métodos:
- Investigó el efecto de la interleucina-2 en la fosforilación y activación de la p70 S6 quinasa, la MAP quinasa (ERK) y la S6 quinasa (RSK).
- Se evaluó el impacto de la rapamicina en la activación de la quinasa p70 S6 inducida por la interleucina-2.
- Se examinó la interacción entre la rapamicina, FK506 y FKBP.
Principales resultados:
- La interleucina-2 estimula selectivamente la fosforilación y activación de la quinasa p70 S6, pero no la ERK ni la RSK.
- La rapamicina inhibe rápida y completamente la activación de la quinasa p70 S6 inducida por la interleucina-2 a bajas concentraciones (0,05-0,2 nM).
- FK506 antagoniza de manera competitiva los efectos de la rapamicina, lo que indica una mediación a través de FKBP.
Conclusiones:
- El complejo rapamicina-FKBP bloquea selectivamente la cascada de activación de la quinasa p70 S6.
- Esta vía de señalización está implicada en la regulación de la entrada de las células T en la fase S.
- Los efectos inmunosupresores de la rapamicina están relacionados con la inhibición de la señalización de la quinasa p70 S6.
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