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El desacoplamiento de Grb2 del receptor Met in vivo revela funciones complejas en el desarrollo muscular

F Maina¹, F Casagranda, E Audero

¹European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.

|November 1, 1996

Resumen

La señalización del factor de crecimiento hepatocitario (HGF) a través de su receptor Met requiere tirosinas específicas para el desarrollo. La alteración de estos sitios afecta a la placenta, el hígado y el músculo, revelando el papel de Met en la formación tardía del músculo.

Área de la Ciencia:

Biología Molecular Biología Molecular
Biología del desarrollo Biología del desarrollo.
Genética La genética.

Sus antecedentes:

El factor de crecimiento hepatocitario (HGF) y su receptor, la Met tirosina quinasa, son cruciales para el desarrollo.
La señalización met es esencial para la formación de la placenta, el hígado y los músculos.
Los mecanismos precisos de la señalización Met in vivo no se comprenden completamente.

Objetivo del estudio:

Investigar el requisito in vivo de la señalización de Met a través de sus tirosinas carboxiterminales.
Para aclarar las funciones específicas de las vías de señalización Met en diferentes tejidos.
Identificar nuevas funciones de la señalización HGF/Met en la miogénesis.

Principales métodos:

Generación de ratones mutantes con mutaciones específicas en las tirosinas Met carboxiterminales.
Análisis fenotípico de embriones mutantes, centrado en el desarrollo de la placenta, el hígado y los músculos.
Evaluación de la interrupción de enlace Grb2 y su impacto en la señalización Met.

Principales resultados:

La mutación de ambas tirosinas carboxiterminales en Met causó letalidad embrionaria con graves defectos en la placenta, el hígado y los músculos de las extremidades.
La interrupción de los sitios de unión de Grb2 permitió el desarrollo del término, pero resultó en una reducción del músculo de la extremidad y menos fibras secundarias.
Estos hallazgos indican requisitos específicos del tejido para las vías de señalización Met.

Conclusiones:

La función met en vivo depende de la señalización a través de dos tirosinas carboxiterminales críticas.
La señalización HGF/Met juega un papel vital y previamente no reconocido en las últimas etapas de la miogénesis.
El estudio pone de relieve los requisitos diferenciales de la señalización Met en varios contextos de desarrollo.

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