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Las distintas fosfotirosinas en un receptor del factor de crecimiento se unen a moléculas específicas que median
W J Fantl1, J A Escobedo, G A Martin
1Howard Hughes Medical Institute, University of California, San Francisco 94143.
Cell
|May 1, 1992
Resumen
El receptor del factor de crecimiento derivado de plaquetas (PDGF) se une a la proteína activadora de la GTPasa (GAP) y a la fosfatidilinositol 3-quinasa (PI3-quinasa) en sitios distintos. Estas interacciones son cruciales para la síntesis de ADN estimulada por PDGF.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La señalización celular de las células.
Sus antecedentes:
- El receptor del factor de crecimiento derivado de plaquetas (PDGF) es un regulador clave del crecimiento y la proliferación celular.
- Interactúa con las proteínas de señalización intracelular como la proteína activadora de la GTPasa (GAP) y la fosfatidilinositol 3-kinasa (PI3-kinasa), que contienen dominios SH2.
Objetivo del estudio:
- Para identificar los sitios específicos de unión en el receptor PDGF para PI3-cinasa y GAP.
- Para aclarar el significado funcional de estas interacciones en la señalización mediada por PDGF.
Principales métodos:
- Utilizó péptidos que contienen fosfotirosina que representan secuencias de receptores PDGF para inhibir competitivamente la PI3-cinasa y la unión GAP.
- Se introdujeron mutaciones puntuales en sitios de unión identificados en el receptor del PDGF.
Principales resultados:
- La PI3-cinasa se une a dos residuos distintos de fosfotirosina dentro de motivos de secuencia específicos en el receptor del PDGF.
- Las mutaciones en estos sitios de unión a la PI3-cinasa abolieron la asociación de la PI3-cinasa y deterioraron la síntesis de ADN estimulada por PDGF.
- La mutación del sitio de unión GAP interrumpió la asociación GAP y la fosforilación, pero no afectó la unión a la PI3-cinasa ni afectó significativamente la síntesis de ADN.
Conclusiones:
- GAP y PI3-cinasa se unen a motivos de secuencia separados que contienen fosfotirosina en el receptor PDGF.
- Los sitios de unión de la PI3-cinasa son críticos para mediar la síntesis de ADN estimulada por PDGF, mientras que el sitio de unión de GAP tiene un papel menor.
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