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Src tirosina quinasa es un nuevo efector directo de las proteínas G
1Department of Physiology, Cornell University Medical College, New York, New York 10021, USA.
Cell
|September 28, 2000
Resumen
Las proteínas G regulan directamente las kinasas de la familia Src. Las subunidades G alfa específicas (Galphas y Galphai) activan las tirosinacinasas Src y Hck al unirse a sus dominios catalíticos, revelando una nueva vía de señalización.
Área de la Ciencia:
- Señalización celular y biología molecular.
- Regulación de la proteína tirosina quinasa regulación de las proteínas tirosina quinasa
- Las vías de los receptores acoplados a proteínas G.
Sus antecedentes:
- Las proteínas G heterotriméricas son transductores clave de señales desde los receptores de la superficie celular hasta los efectores.
- Src, un proto-oncogén y proteína tirosina quinasa, es crucial en la señalización del receptor acoplado a la proteína G.
- El mecanismo bioquímico preciso que vincula la regulación de la proteína G a la actividad del Src no estaba claro.
Objetivo del estudio:
- Aclarar el mecanismo por el cual las proteínas G regulan bioquímicamente la actividad de la Src quinasa.
- Para identificar subunidades específicas de proteínas G involucradas en la modulación de la actividad Src.
- Determinar si esta regulación se extiende a otras cinasas de la familia Src.
Principales métodos:
- Pruebas in vitro de quinasa para medir la actividad de c-Src. regulado a la baja.
- Prueba del efecto de varias subunidades G alfa (Galphas, Galphai, Galphaq, Galpha12) y Gbeta gamma (Gbetay) en la actividad de la quinasa.
- Ensayos bioquímicos para evaluar la unión de las proteínas G al Src y los cambios conformacionales.
Principales resultados:
- Galphas y Galphai estimulan directamente la actividad de la quinasa del c-Src. regulado a la baja.
- Galphaq, Galpha12 y Gbetay no mostraron estimulación significativa de la actividad c-Src.
- Galphas y Galphai también modulan Hck, otra tirosina quinasa de la familia Src, al unirse a su dominio catalítico y alterar su conformación para aumentar la accesibilidad al sustrato.
Conclusiones:
- Las tirosinacinasas de la familia Src son efectores directos aguas abajo de proteínas G específicas (Galphas y Galphai).
- La unión de la proteína G al dominio catalítico de las cinasas Src induce cambios conformacionales que mejoran su actividad.
- Este estudio revela un nuevo mecanismo de transducción de señales que vincula las vías de la proteína G a la fosforilación de la tirosina mediada por Src.
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