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Updated: Jul 13, 2026
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
La afinidad del receptor EGF está regulada por el calcio intracelular y la proteína quinasa C
Cell
|April 1, 1985
Resumen
Los ésteres de forbol inhiben la unión del factor de crecimiento epidérmico (EGF) a los receptores de la superficie celular mediante la activación de la proteína quinasa C. Este proceso dependiente del calcio, crucial en las células intactas, implica la fosforilación del receptor EGF.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- La señalización del receptor del factor de crecimiento epidérmico (EGF) es fundamental para el crecimiento y la diferenciación celular.
- Se sabe que los ésteres de Phorbol modulan los procesos celulares, incluida la función del receptor.
Objetivo del estudio:
- Investigar el mecanismo por el cual los ésteres de forbol inhiben la unión del FEG a su receptor.
- Para aclarar el papel del calcio intracelular y la proteína quinasa C en esta modulación.
Principales métodos:
- Tratamiento de las células intactas con phorbol myristate acetate (PMA).
- Aislamiento de las membranas celulares y medición de la unión 125I-EGF.
- Manipulación de los niveles de calcio intracelular utilizando EGTA y A23187.7.
- Reconstitución de las membranas aisladas con proteína quinasa C. purificada.
Principales resultados:
- Los ésteres de forbol redujeron la unión del EGF en células intactas, pero no en membranas aisladas.
- Los niveles intracelulares de calcio modulan la afinidad del receptor EGF.
- La activación de la proteína quinasa C fue necesaria para la inhibición inducida por el éster de forbol de la unión al EGF.
- La reconstitución con proteína quinasa C restauró la sensibilidad al éster de forbol y alteró la fosforilación del receptor EGF.
Conclusiones:
- La activación de la proteína kinasa C dependiente del calcio por los ésteres de forbol modula la afinidad del receptor EGF en células intactas.
- Esta modulación es probablemente mediada por una fosforilación alterada del receptor del FEAG.
- Los hallazgos destacan la importancia de las vías de señalización intracelular en la regulación de la función del receptor del factor de crecimiento.
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