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Necesidad de activina A y factor de crecimiento transformador--pro-regiones beta 1 en el ensamblaje homodímero
1Department of Developmental Biology, Genentech, Inc., South San Francisco, CA 94080.
Science (New York, N.Y.)
|March 16, 1990
Resumen
La pro-región es esencial para el plegamiento adecuado, la formación de enlaces disulfuro y la secreción del factor de crecimiento transformador-beta 1 (TGF-beta 1) y los homodímeros de activina A. Se requiere la coexpresión de la pro-región con regiones maduras para la formación y exportación de dímeros biológicamente activos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biosíntesis de las proteínas Biosíntesis de las proteínas.
Sus antecedentes:
- Muchas proteínas se sintetizan como precursores inactivos.
- El factor de crecimiento transformador-beta 1 (TGF-beta 1) y la activina A son homodímeros estructuralmente relacionados vinculados al disulfuro.
- La función de la pro-región en la biosíntesis de estas proteínas no se entiende completamente.
Objetivo del estudio:
- Investigar el papel de la pro-región en la biosíntesis del TGF-beta 1 y la activina A.
- Para determinar si la pro-región es necesaria para el plegamiento adecuado, la formación de enlaces disulfuro y la secreción de estos homodímeros.
Principales métodos:
- Utilizamos vectores de expresión para expresar ya sea la pro-región o las regiones maduras de TGF-beta 1 y activina A.
- Realizó experimentos de complementación para evaluar la función de la pro-región en conjunto con las regiones maduras.
- Se evaluó la dimerización intracelular y la secreción de homodímeros biológicamente activos.
Principales resultados:
- La dimerización intracelular y la secreción de homodímeros biológicamente activos de TGF-beta 1 y activina A solo se produjeron cuando la pro-región se coexpresó con la región madura.
- Se descubrió que las pro-regiones son cruciales para la formación de enlaces plegables y disulfuro de sus respectivos homodímeros.
- Las pro-regiones facilitan la exportación de homodímeros de TGF-beta 1 y activina A.
Conclusiones:
- Las pro-regiones de TGF-beta 1 y la activina A juegan un papel crítico en la biosíntesis adecuada de estas proteínas.
- Las pro-regiones son esenciales para el plegamiento correcto, la formación de enlaces disulfuro y la secreción de homodímeros biológicamente activos.
- Comprender el papel de las pro-regiones puede informar estrategias terapéuticas que involucran TGF-beta 1 y vías de señalización de activina A.
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