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Acoplamiento conformal a través de la membrana plasmática en la activación del receptor del FEAG
Nicholas F Endres1, Rahul Das, Adam W Smith
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|February 5, 2013
Resumen
La activación del receptor del factor de crecimiento epidérmico (EGFR) depende de la densidad de su superficie. La unión del FEAG libera las restricciones estéricas, promoviendo las interacciones de la hélice transmembrana y la activación del receptor.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los mecanismos de activación del receptor del factor de crecimiento epidérmico (EGFR) no se comprenden completamente.
- El dominio intracelular del EGFR exhibe actividad intrínseca en solución.
Objetivo del estudio:
- Para investigar la regulación de la activación del EGFR.
- Determinar el papel de la densidad superficial del EGFR en la autofosforilación.
Principales métodos:
- Medición de la autofosforilación del EGFR en función de la densidad de la superficie en las células.
- Espectroscopia de fluorescencia de correlación cruzada para evaluar la dimerización.
- Resonancia Magnética Nuclear (RMN) y ensayos funcionales.
Principales resultados:
- EGFR escapa de la inhibición sólo en altas densidades superficiales sin EGF.
- La hélice transmembrana y el módulo intracelular juntos permiten la actividad constitutiva.
- El módulo intracelular aislado se inactiva y no se dimeriza cuando está atado a la membrana.
- La activación requiere la interacción de la hélice transmembrana N-terminal, promoviendo la interacción del segmento de juxtamembrana y la liberación de la membrana.
Conclusiones:
- La unión del FEAG alivia las restricciones estéricas extracelulares.
- Esto promueve la activación a través de la asociación N-terminal de las hélices transmembrana.
- La activación del EGFR está regulada tanto por la unión al ligando como por la densidad de la superficie del receptor.
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