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La localización nuclear y la actividad de señalización de la fosfoinositidasa C beta en células suizas 3T3
A M Martelli1, R S Gilmour, V Bertagnolo
1Institutes of Human Anatomy, University of Bologna, Italy.
Nature
|July 16, 1992
Resumen
El factor de crecimiento similar a la insulina-1 (IGF-1) desencadena la actividad nuclear de la fosfoinositidasa C, lo que lleva a la descomposición del fosfatidilinositol 4,5-bisfosfato (PtdInsP2). Esta vía de señalización nuclear es crucial para la proliferación celular.
Área de la Ciencia:
- Biología celular Biología celular.
- La señalización molecular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La hidrólisis del fosfatidilinositol 4,5-bisfosfato (PtdInsP2) es una vía clave de señalización de la membrana plasmática.
- La evidencia sugiere un distinto sistema de señalización de fosfoinosítidos nucleares.
- Los niveles de lípidos nucleares de inositol disminuyen con la estimulación del factor de crecimiento similar a la insulina-1 (IGF-1).
Objetivo del estudio:
- Investigar el mecanismo por el cual IGF-1 inicia la descomposición de PtdInsP2 en el núcleo.
- Para identificar la isoenzima específica de la fosfoinositidasa C (PLC) involucrada en la señalización nuclear.
- Determinar el papel del PLC nuclear en las respuestas celulares inducidas por el IGF-1.
Principales métodos:
- Investigó la síntesis de fosfoinosítidos nucleares in vitro.
- Cambios monitoreados en el lípido de inositol nuclear y la masa de diacilglicerol en respuesta al IGF-1.
- Examinó la localización y la actividad de las isozimas PLC (beta y gamma) en las células 3T3.
- Evaluó la respuesta mitogénica de las células que expresan el receptor de IGF-1.
Principales resultados:
- Los núcleos purificados sintetizan el PtdInsP2 y el fosfatidilinositol 4-fosfato (PtdInsP).
- El tratamiento con IGF-1 causa una disminución transitoria en los niveles nucleares de PtdInsP y PtdInsP2.
- El diacilglicerol nuclear aumenta, precediendo a la activación y translocación de la proteína kinasa C.
- Los núcleos de las células 3T3 contienen la beta-isozima de la fosfoinositidasa C.
- El IGF-1 estimula la actividad de la fosfoinositidasa nuclear C exclusivamente.
Conclusiones:
- Existe un distinto sistema de señalización de fosfoinosítidos nucleares, regulado por el IGF-1.
- La beta-isozima de la fosfoinositidasa C está localizada en el núcleo y es activada por el IGF-1.
- La activación del PLC nuclear es un paso crítico en la señalización mediada por IGF-1 que conduce a la proliferación celular.
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