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Transformación celular y activación de pp60c-src por la sobreexpresión de una proteína tirosina fosfatasa
X M Zheng1, Y Wang, C J Pallen
1Cell Regulation Laboratory, National University of Singapore.
Nature
|September 24, 1992
Resumen
La sobreexpresión de la proteína tirosina fosfatasa alfa (PTPα) activa persistentemente la quinasa pp60c-src, lo que lleva a la transformación celular y la tumorigénesis. Esta activación implica la desfosforilación del sitio regulador negativo Tyr527.
Área de la Ciencia:
- Biología celular Biología celular.
- Oncología Molecular Oncología Molecular
- Transducción de señales Transducción de señales.
Sus antecedentes:
- La actividad de la quinasa pp60c-src está estrictamente regulada durante el ciclo celular, aumentando normalmente durante la mitosis.
- La desregulación de pp60c-src, a menudo a través de mutaciones u oncoproteínas virales, conduce a un crecimiento celular incontrolado y al cáncer.
- El sitio carboxiterminal Tyr527 es crucial para la regulación negativa de la actividad de la quinasa pp60c-src.
Objetivo del estudio:
- Para investigar el papel de la proteína tirosina fosfatasa alfa (PTPα) en la regulación de la actividad de la quinasa pp60c-src.
- Para determinar si la sobreexpresión de PTPα puede inducir la transformación celular y la tumorigénesis.
- Para dilucidar el mecanismo por el cual PTPα afecta la actividad pp60c-src.
Principales métodos:
- Sobreexpresión de PTPα en las células.
- Evaluación de la actividad de la quinasa pp60c-src.
- Analizando el estado de fosforilación de Tyr527.
- Ensayos de desfosforilación in vitro con PTPα purificado.
Principales resultados:
- La sobreexpresión de PTPα dio lugar a una activación persistente de la quinasa pp60c-src.
- La sobreexpresión de PTPα condujo a la transformación celular y la tumorigénesis.
- La activación de pp60c-src en las células sobreexpresoras de PTPα se asoció con la desfosforilación en Tyr527.
- PTPα purificado Tyr527 directamente desfosforilado de pp60c-src en in vitro.
Conclusiones:
- PTPα juega un papel importante en la regulación de la proliferación celular.
- PTPα ejerce sus efectos, al menos en parte, a través de la activación de la quinasa pp60c-src.
- La sobreexpresión de PTPα posee capacidad oncogénica, contribuyendo a la tumorigénesis a través de la activación de pp60c-src.
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