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Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
Una pantalla de RNAi funcional para los reguladores del receptor tirosina quinasa y la señalización ERK
Adam Friedman1, Norbert Perrimon
1Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Nature
|November 7, 2006
Resumen
Este estudio utilizó una pantalla de interferencia de ARN de todo el genoma en Drosophila para identificar nuevos reguladores de la señalización de la quinasa regulada por señal extracelular (ERK). La pantalla reveló 331 reguladores de vías conservadas, incluida una quinasa similar a Ste20 y una fosfatasa de la familia PPM, destacando posibles objetivos farmacológicos.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La señalización de la receptor tirosina quinasa (RTK) y la cinasa regulada por la señal extracelular (ERK) son cruciales para el desarrollo de metazoos y están implicadas en enfermedades como el cáncer.
- Si bien se conocen los componentes centrales de RTK / ERK, es probable que exista una red reguladora más amplia, con muchos genes no descubiertos debido a las limitaciones de los métodos de detección tradicionales.
Objetivo del estudio:
- Realizar una evaluación imparcial de todo el genoma para identificar nuevos reguladores de la señalización RTK/ERK.
- Para obtener una visión global de los procesos celulares integrados por la vía ERK salida.
- Validar y clasificar los reguladores identificados por su relevancia in vivo y en células de mamíferos.
Principales métodos:
- Se realizó una pantalla de interferencia de ARN (RNAi) de alto rendimiento en todo el genoma en células de Drosophila.
- Utilizó un nuevo ensayo celular cuantitativo para monitorear la activación de ERK.
- Realizó análisis adicionales de componentes seleccionados a través de múltiples tipos celulares y estímulos.
Principales resultados:
- Identificaron y validaron 331 nuevos reguladores de la señalización RTK/ERK.
- Se demostró que la salida de la vía ERK integra diversos procesos celulares conservados.
- Se aisló una quinasa similar a Ste20 y una fosfatasa de la familia PPM que regulan la señalización de RTK / ERK in vivo y en células de mamíferos.
Conclusiones:
- La vía de señalización RTK / ERK está regulada por una gran red de proteínas conservadas.
- Los nuevos reguladores identificados en este estudio representan posibles objetivos terapéuticos para enfermedades asociadas con la señalización aberrante de RTK / ERK.
- Esta investigación proporciona un recurso integral para comprender la regulación de la vía RTK / ERK y el descubrimiento de fármacos.
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