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Los precursores transmembranares del TGF-alfa activan los receptores del EGF y el TGF-alfa
R Brachmann1, P B Lindquist, M Nagashima
1Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Cell
|February 24, 1989
Resumen
Las formas transmembranares del precursor del factor de crecimiento transformador alfa (TGF-alfa) activan el receptor del factor de crecimiento epidérmico (EGF). Estas formas de TGF-alfa ligadas a la membrana promueven el crecimiento celular y pueden desempeñar un papel en la comunicación intercelular en los tejidos proliferantes.
Área de la Ciencia:
- Biología celular Biología celular.
- La señalización molecular.
- Investigación de la investigación del cáncer.
Sus antecedentes:
- El factor de crecimiento transformador alfa (TGF-alfa) y el factor de crecimiento epidérmico (EGF) son factores de crecimiento relacionados que activan un receptor común.
- La escisión proteolítica libera TGF-alfa soluble, pero también existen formas unidas a la membrana en las superficies celulares.
Objetivo del estudio:
- Para investigar la actividad biológica de las formas de precursores de TGF-alfa ligados a la membrana.
- Para determinar si estas formas pueden activar el receptor EGF/TGF-alfa e influir en la proliferación celular.
Principales métodos:
- Modificación genética del precursor de TGF-alfa para evitar la escisión.
- Sobreexpresión del ADNc modificado en las células receptor-negativas.
- Purificación parcial y secuenciación N-terminal de las formas de TGF-alfa.
- Pruebas para la autofosforilación del receptor y el crecimiento celular independiente del anclaje.
Principales resultados:
- Se identificaron dos formas de precursores transmembranares del TGF-alfa.
- Estas formas indujeron la autofosforilación de la tirosina del receptor EGF/TGF-alfa en las células que sobreexpresan el receptor.
- Los precursores disueltos promovieron el crecimiento independiente del anclaje de los fibroblastos.
- El contacto célula-célula también condujo a la activación del receptor.
Conclusiones:
- Las formas transmembranares del precursor TGF-alfa poseen actividad biológica.
- Pueden activar el receptor EGF/TGF-alfa y estimular la proliferación celular.
- Estos hallazgos sugieren un papel para el TGF-alfa ligado a la membrana en las interacciones célula-célula dentro de los tejidos proliferantes.
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