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Vinculación de GAP a los receptores activados de PDGF
A Kazlauskas1, C Ellis, T Pawson
1Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Science (New York, N.Y.)
|March 30, 1990
Resumen
La señalización del factor de crecimiento derivado de plaquetas (PDGF) involucra a la proteína activadora de Ras GTPase (GAP). La unión de PDGF a su receptor recluta GAP, que requiere actividad de receptor quinasa y sitios específicos de fosforilación de tirosina para una asociación máxima.
Área de la Ciencia:
- Las vías de señalización celular.
- Biología molecular La biología molecular.
- La investigación en el oncogén se basa en la investigación oncogénica.
Sus antecedentes:
- Los productos del proto-oncogén Ras son transductores de señales intracelulares clave.
- La proteína activadora de Ras GTPasa (GAP) media las señales de Ras.
- Los receptores del factor de crecimiento derivado de plaquetas (PDGF) inician cascadas de señalización tras la unión de ligandos.
Objetivo del estudio:
- Para investigar la interacción entre los receptores de PDGF y GAP.
- Para aclarar los requisitos moleculares para la asociación de GAP con el receptor PDGF.
Principales métodos:
- Utilizó células epiteliales de perro diseñadas para expresar receptores humanos de PDGF.
- Estudió el efecto de la unión del PDGF en la formación del complejo GAP.
- Empleó receptores mutantes de PDGF para identificar dominios y actividades críticas para la asociación receptor-GAP.
Principales resultados:
- La unión de PDGF indujo la formación de complejos entre GAP y el receptor de PDGF en aproximadamente el 10% del total de moléculas de GAP.
- La asociación máxima de GAP con el receptor requería la función activa de la receptor quinasa.
- Los residuos de tirosina fosforilables específicos en los sitios de autofosforilación fueron esenciales para una complejación GAP robusta.
Conclusiones:
- La interacción entre los receptores de PDGF y el GAP es un paso crítico en la señalización intracelular mediada por PDGF.
- La actividad de la receptor quinasa y los sitios específicos de fosforilación de tirosina son indispensables para el reclutamiento eficiente de GAP.
- Esta interacción pone de relieve la intrincada regulación de las vías de señalización Ras por parte de los receptores del factor de crecimiento.
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