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El proto-oncogén trk codifica un receptor para el factor de crecimiento nervioso
1Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Cell
|April 5, 1991
Resumen
El producto del proto-oncogén trk, gp140trk, funciona como un receptor del factor de crecimiento nervioso (NGF) de alta afinidad. Este receptor media la señalización del NGF, incluida la fosforilación de la tirosina y la actividad de la quinasa, independientemente de los receptores de baja afinidad en las células no neuronales.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La señalización celular de las células.
Sus antecedentes:
- Existen dos receptores distintos del factor de crecimiento nervioso (NGF): un receptor de baja afinidad (LNGFR) y un receptor de alta afinidad cuya estructura se desconoce.
- El receptor de baja afinidad es una glicoproteína rica en cisteína codificada por el gen LNGFR.
Objetivo del estudio:
- Para identificar la naturaleza estructural del receptor NGF de alta afinidad.
- Investigar el papel funcional del producto trk proto-oncogénico (gp140trk) en la unión y señalización del NGF.
Principales métodos:
- Experimentos de enlace cruzado químico para detectar la unión de NGF a gp140trk.
- Análisis de la expresión de gp140trk en varios tipos de células (PC12, fibroblastos de ratón, células Sf9 de insectos).
- Evaluación de la gp140trk fosforilación de la tirosina y la actividad de la tirosina quinasa tras la estimulación del NGF.
Principales resultados:
- El producto del proto-oncogén trk humano, gp140trk, se une al NGF con una alta afinidad (Kd ~ 10^-11 a 10^-10 M).
- NGF puede ser enlazado a gp140trk en múltiples tipos de células, incluidas las que carecen de LNGFR.
- La estimulación del NGF induce una rápida fosforilación de la tirosina y activa la actividad de la tirosina quinasa de gp140trk.
Conclusiones:
- gp140trk es un receptor funcional de NGF de alta afinidad.
- gp140trk media en las vías críticas de transducción de señales del NGF, incluida la activación de la tirosina quinasa.
- La unión de NGF de alta afinidad a gp140trk puede ocurrir independientemente del LNGFR en células no neuronales.
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