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La señalización nuclear por las receptoras tirosina quinasas: el primer petirrojo de la primavera
Joseph Schlessinger1, Mark A Lemmon
1Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. joseph.schlessinger@yale.edu
Cell
|October 5, 2006
Resumen
Las receptoras tirosina quinasas (RTKs) pueden señalar dentro del núcleo. Un fragmento del receptor ErbB4 se mueve al núcleo, formando un complejo que reprime la transcripción génica que promueve los astrocitos.
Área de la Ciencia:
- La señalización celular de las células.
- Biología molecular La biología molecular.
- La neurociencia es la neurociencia.
Sus antecedentes:
- Las receptoras tirosina quinasas (RTK) son clave en la señalización transmembrana.
- Las funciones nucleares de las RTK, en particular la translocación dependiente de ligandos, no se comprenden completamente.
- ErbB4 es una RTK implicada en varios procesos celulares.
Objetivo del estudio:
- Para investigar la importancia funcional de los fragmentos de receptores ErbB4 intracelulares en el núcleo.
- Para dilucidar los mecanismos moleculares de la señalización nuclear ErbB4.
- Determinar el impacto de la señalización nuclear ErbB4 en la expresión génica, específicamente en la formación de astrocitos.
Principales métodos:
- Estimulación por ligandos de los receptores ErbB4.
- Análisis de la translocación del fragmento del receptor al núcleo.
- Coinmunoprecipitación para identificar complejos de proteínas (fragmento de ErbB4, TAB2, N-CoR).
- Análisis cuantitativo de los cambios en la expresión génica en el núcleo utilizando técnicas como la RT-qPCR.
- Los ensayos del reportero para evaluar la represión transcripcional.
Principales resultados:
- La activación del ligando libera un fragmento de receptor ErbB4 intracelular.
- Este fragmento se transloca al núcleo.
- El fragmento ErbB4 forma un complejo funcional con el adaptador TAB2 y el corepressor N-CoR.
- El complejo nuclear reprime la transcripción de los genes involucrados en la formación de astrocitos.
Conclusiones:
- Los fragmentos intracelulares del receptor ErbB4 pueden participar en la señalización nuclear directa.
- La señalización nuclear ErbB4, mediada por un complejo con TAB2 y N-CoR, juega un papel en la represión transcripcional.
- Esta vía de señalización nuclear influye en la expresión génica relacionada con el desarrollo de los astrocitos, lo que sugiere un papel novedoso para las RTK más allá de la membrana celular.
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