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Complementación del activador mitótico, p80cdc25, por una proteína humana tirosina fosfatasa por una proteína humana
Science (New York, N.Y.)
|December 14, 1990
Resumen
La entrada mitótica requiere la activación de la proteína quinasa pp34. Este estudio muestra que la desfosforilación de Tyr15 desencadena la activación del complejo pp34-ciclina, que involucra a una proteína humana tirosina fosfatasa y la vincula a la vía cdc25.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología molecular La biología molecular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El inicio de la fase M depende de la activación de la proteína quinasa pp34 en los eucariotas.
- En Schizosaccharomyces pombe, la fosforilación por Tyr15 de pp34 regula el inicio de la mitosis.
- La desfosforilación de Tyr15 es un paso regulador clave para la progresión del ciclo celular.
Objetivo del estudio:
- Para investigar el papel de la desfosforilación de Tyr15 en la activación de pp34.
- Para identificar la fosfatasa responsable de la desfosforilación de Tyr15.
- Para aclarar la conexión entre la desfosforilación de la tirosina y la vía cdc25.
Principales métodos:
- En ensayos in vitro e in vivo utilizando levadura de fisión y fosfatasa de proteína tirosina humana.
- Análisis de la activación del complejo pp34-ciclina.
- Análisis de ADN complementario (ADNc) para evaluar el reemplazo de la vía.
Principales resultados:
- La desfosforilación de Tyr15 desencadena directamente la activación del complejo pp34-ciclina en las levaduras de fisión.
- Una proteína tirosina fosfatasa humana cataliza efectivamente este evento de desfosforilación.
- La activación del pp34 no requiere necesariamente la desfosforilación de la treonina.
- El cDNA de la tirosina fosfatasa reemplazó funcionalmente a p80cdc25, lo que indica una asociación de vías.
Conclusiones:
- La desfosforilación de tirosina es un evento crítico para iniciar la mitosis mediante la activación del complejo pp34-ciclina.
- Las fosfatasas de proteína-tirosina humanas pueden realizar esta función reguladora, lo que sugiere mecanismos conservados.
- Los hallazgos establecen un vínculo directo entre la desfosforilación por tirosina de pp34 y la vía de activación mitótica mediada por cdc25.
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