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La activación de la p70/p85 S6 quinasa por una vía independiente de la p21ras
X F Ming1, B M Burgering, S Wennström
1Friedrich Miescher Institute, Basel, Switzerland.
Nature
|September 29, 1994
Resumen
La vía de señalización p70s6k/p85s6k, crucial para el crecimiento celular, es independiente de la p21ras. Esta vía diverge de la vía p21ras a nivel del receptor y es iniciada por la autofosforilación.
Área de la Ciencia:
- Las vías de señalización celular.
- Biología molecular La biología molecular.
- La señalización de la quinasa.
Sus antecedentes:
- p70s6k y p85s6k son isoformas de una quinasa vital para la mitogénesis.
- Su activación implica una fosforilación compleja y una vía de señalización distinta de la de p42mapk/p44mapk.
- La activación de p42mapk/p44mapk está aguas abajo de Sos, p21ras, p74raf y p47mek.
Objetivo del estudio:
- Para investigar si la vía de señalización p70s6k/p85s6k diverge de la vía p21ras.
- Para determinar el punto de bifurcación entre estas dos cascadas de señalización.
Principales métodos:
- Utilizando mutantes de p74raf y p21ras para evaluar su impacto en la activación de p44mapk y p70s6k.
- Analizando la señalización en las células que expresan receptores de factor de crecimiento derivados de plaquetas humanas modificados (falto de dominio de inserción de quinasa).
- Identificación de sitios críticos de autofosforilación dentro del dominio del receptor.
Principales resultados:
- Los mutantes de p74raf y p21ras inhibieron la activación de p44mapk pero no la activación de p70s6k.
- Se observó activación del factor de crecimiento p21ras, pero no p70s6k/p85s6k, en células con receptores de PDGF modificados.
- El residuo de tirosina 751 fue identificado como un sitio crítico de autofosforilación para la activación de p70s6k/p85s6k.
Conclusiones:
- La vía de señalización p70s6k/p85s6k es independiente de la p21ras.
- El punto de divergencia entre las vías p70s6k/p85s6k y p21ras se encuentra a nivel de los receptores.
- La iniciación de la vía p70s6k/p85s6k se produce a través de la autofosforilación en un sitio específico (Tyr751).
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