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La fosforilación por tirosina del producto vav proto-oncogénico en las células B activadas
1Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Science (New York, N.Y.)
|May 22, 1992
Resumen
La activación de los linfocitos B implica la fosforilación por tirosina de p95vav, una proteína vinculada al proto-oncogén vav. Esta fosforilación y la asociación con Vap-1 son rápidas, lo que sugiere vav vav.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología Molecular Biología Molecular
- La señalización celular de las células.
Sus antecedentes:
- Los linfocitos B se activan a través de sus receptores de antígeno de inmunoglobulina M (IgM).
- Esta activación desencadena cascadas de señalización intracelular, incluida la fosforilación de la proteína tirosina.
- El producto del proto-oncogén vav, p95vav, es una proteína clave involucrada en estas vías de señalización.
Objetivo del estudio:
- Para investigar el papel de p95vav en la activación de los linfocitos B sobre el compromiso del receptor de IgM.
- Para determinar la cinética y las dependencias de la fosforilación de tirosina p95vav.
- Explorar la interacción de p95vav con otras moléculas de señalización durante la activación de las células B.
Principales métodos:
- El enlace cruzado de la inmunoglobulina M (IgM) en los linfocitos B.
- Análisis de la fosforilación de la proteína tirosina utilizando anticuerpos específicos.
- Evaluación de las interacciones proteína-proteína a través de la coinmunoprecipitación.
- Investigando el papel de los dominios de homología Src 2 (SH2) en las interacciones de proteínas.
Principales resultados:
- La fosforilación por tirosina de p95vav ocurre rápidamente (en cuestión de segundos) después de la vinculación cruzada de IgM.
- La fosforilación p95vav es independiente de la activación de la proteína quinasa C, la señalización de la proteína G y la movilización del calcio.
- p95vav se asocia rápidamente con una proteína fosforilada por tirosina de 70 kDa, Vap-1, en aproximadamente 5 segundos.
- Esta asociación es transitoria, dura unos 60 segundos, y está mediada por el dominio SH2 de p95vav.
Conclusiones:
- El producto del proto-oncogén vav, p95vav, es un receptor de respuesta temprana en la señalización del receptor de antígeno de linfocitos B.
- La fosforilación p95vav y su interacción con Vap-1 son eventos tempranos críticos en la activación de las células B.
- Estos hallazgos ponen de relieve el papel significativo del proto-oncogén vav en la mediación de la activación de los linfocitos B inducida por antígenos.
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