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El precursor de TGF-alfa expresado en la superficie celular se une al receptor de EGF en las células adyacentes, lo

S T Wong¹, L F Winchell, B K McCune

¹Lineberger Cancer Research Center, University of North Carolina School of Medicine, Chapel Hill 27514.

|February 10, 1989

Resumen

La forma precursora del factor de crecimiento transformador alfa (TGF-alfa) puede activar los receptores del factor de crecimiento epidérmico (EGF) en las células adyacentes, incluso sin ser completamente procesado. Este proTGF-alfa unido a la membrana demuestra actividad biológica, impactando las vías de señalización celular.

Área de la Ciencia:

Biología Molecular Biología Molecular
La señalización celular de las células.
Investigación del cáncer Investigación del cáncer.

Sus antecedentes:

El factor de crecimiento transformador alfa (TGF-alfa) generalmente se libera por escisión proteolítica de un precursor unido a la membrana.
La actividad de la proteasa es a menudo un paso que limita la velocidad en la maduración del TGF-alfa, particularmente en las células tumorales.

Objetivo del estudio:

Para investigar la actividad biológica de la forma de precursor ligado a la membrana de TGF-alfa (proTGF-alfa) antes de la escisión proteolítica.
Determinar si el proTGF-alfa puede ejercer efectos biológicos independientemente de su forma madura y secretada.

Principales métodos:

Se introdujeron sustituciones de aminoácidos en los sitios de escisión proteolítica de TGF-alfa dentro de un vector de expresión.
Las células BHK fueron transfectadas con estas secuencias alteradas, impidiendo la secreción madura de TGF-alfa.
Se realizaron experimentos de co-incubación con células BHK que expresan la superficie celular proTGF-alfa y células A431 que expresan los receptores EGF.

Principales resultados:

Las células BHK transfectadas expresaron altos niveles de proTGF-alfa de la superficie celular, pero no secretaron TGF-alfa maduro.
El proTGF-alfa unido a la membrana se une con éxito a los receptores del factor de crecimiento epidérmico (EGF) en las células A431 adyacentes.
Esta interacción indujo la autofosforilación del receptor EGF y un subsiguiente aumento rápido de los niveles de calcio intracelular en las células A431.

Conclusiones:

La forma precursora ligada a la membrana del TGF-alfa (proTGF-alfa) posee actividad biológica intrínseca.
ProTGF-alfa puede activar directamente los receptores del FEAG en las células vecinas sin requerir un procesamiento proteolítico.
Estos hallazgos sugieren que los precursores de membrana integral de los factores de crecimiento pueden tener funciones biológicas significativas.

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