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Activación específica de las fosfatasas de tirosina cdc25 por ciclinas tipo B: evidencia de múltiples funciones de
1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Cell
|December 20, 1991
Resumen
Se identificaron dos nuevos genes humanos CDC25, cdc25A y cdc25B. Ellos activan la tirosina fosfatasa y son regulados por ciclinas tipo B, cruciales para el control del ciclo celular.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- El producto del gen CDC25 es un regulador clave de la progresión del ciclo celular.
- La fosforilación de la tirosina juega un papel crítico en el control del ciclo celular.
Objetivo del estudio:
- Para identificar y caracterizar nuevos genes humanos CDC25.
- Para investigar los mecanismos reguladores de la actividad de la tirosina fosfatasa CDC25.
Principales métodos:
- Aislamiento genético y rescate funcional de mutantes de levadura de fisión.
- Microinyección de anticuerpos en células HeLa para estudiar la detención mitótica.
- Ensayos in vitro para medir la actividad de la tirosina fosfatasa y las interacciones de las proteínas.
Principales resultados:
- Dos nuevos genes humanos CDC25, cdc25A y cdc25B, fueron aislados y caracterizados funcionalmente.
- cdc25A y cdc25B exhiben actividad de la tirosina fosfatasa, estimulada por ciclinas tipo B (B1, B2) pero no por otros tipos de ciclinas.
- Se observó una asociación entre cdc25A, ciclina B1 y cdc2 en las células HeLa.
- Se identificó un motivo conservado para la interacción de la ciclina en las fosfatasas de tirosina, pero ausente en cdc25.
Conclusiones:
- Las ciclinas de tipo B son multifuncionales, ya que regulan tanto la actividad de la cinasa cdc2 como la activación de la tirosina fosfatasa cdc25.
- cdc25A y cdc25B son componentes clave en la vía de control del ciclo celular, activados por ciclinas de tipo B.
- La interacción intermolecular con la ciclina B probablemente proporciona un dominio de activación a las fosfatasas cdc25.
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