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El complejo endofilina-CIN85-Cbl media la regulación descendente dependiente de los ligandos de c-Met

Annalisa Petrelli¹, Giorgio F Gilestro, Stefania Lanzardo

¹CNR-CIOS and Department of Genetics, Biology and Biochemistry, University of Torino, 10126 Torino, Italy.

|March 15, 2002

Resumen

Un complejo recientemente identificado que involucra a las endofilinas, CIN85 y Cbl regula el factor de crecimiento hepatocitario (HGF) receptor (Met) internalización. Este descubrimiento aclara la señalización del receptor HGF y los mecanismos de endocitosis.

Área de la Ciencia:

Biología celular Biología celular.
Biología Molecular Biología Molecular
Transducción de señales Transducción de señales.

Sus antecedentes:

La regulación a la baja del receptor de la tirosina quinasa es crucial para la modulación de la señalización.
El receptor del factor de crecimiento hepatocitario (HGF) (Met) se somete a poliubiquitinación y degradación al unirse al ligando.
Los mecanismos de la endocitosis del receptor HGF siguen siendo en gran medida desconocidos.

Objetivo del estudio:

Para dilucidar los mecanismos moleculares que rigen el receptor HGF (Met) endocitosis.
Para identificar el complejo proteico responsable de la internalización del receptor HGF.
Investigar el papel de Cbl en la señalización del receptor HGF y la endocitosis.

Principales métodos:

Investigó el papel de las endofilinas, CIN85 y Cbl en la endocitosis del receptor.
Utilizó ensayos bioquímicos para demostrar la formación compleja y las interacciones de unión.
Se evaluó el impacto de la inhibición de la formación de complejos en la internalización y señalización de los receptores HGF.

Principales resultados:

Un complejo de endofilinas, CIN85 y Cbl controla la endocitosis del receptor HGF.
Las endofilinas facilitan la formación de vesículas recubiertas de clatrina y la invaginación de la membrana.
Los ubiquitinatos de Cbl activan el receptor HGF y reclutan el complejo endofilina-CIN85 para su internalización.
La inhibición de este complejo bloquea la internalización del receptor HGF y mejora la señalización.

Conclusiones:

Se reveló un nuevo mecanismo para la endocitosis del receptor HGF (Met) que involucra a las endofilinas, CIN85 y Cbl.
Se estableció un vínculo funcional entre Cbl, señalización de receptores y endocitosis.
Se demostró que la Cbl juega un papel crítico en la regulación de la actividad de los receptores HGF y las respuestas biológicas.

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