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CREB: un factor de transcripción regulado por Ca(2+) fosforilado por las cinasas dependientes de la calmodulina
M Sheng1, M A Thompson, M E Greenberg
1Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Science (New York, N.Y.)
|June 7, 1991
Resumen
Los iones de calcio (Ca2+) desencadenan la inducción génica a través de las cinasas proteicas dependientes de la calmodulina (CaM) que activan el factor de transcripción CREB. La fosforilación de CREB en Ser133 por las cinasas CaM es crucial para esta transducción de la señal eléctrica al núcleo.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La señalización celular de las células.
Sus antecedentes:
- La despolarización de la membrana desencadena respuestas celulares, incluida la inducción génica.
- Los iones de calcio (Ca2+) juegan un papel crítico en la mediación de estas respuestas.
- La proteína de unión al elemento de respuesta de la adenosina 3',5'-monofosfato (cAMP) (CREB) es un factor de transcripción conocido involucrado en la señalización celular.
Objetivo del estudio:
- Investigar el mecanismo por el cual Ca2+ media la inducción génica después de la despolarización de la membrana.
- Determinar el papel de las cinasas proteicas dependientes de Ca(2+) -calmodulina (cinasas CaM) y CREB en este proceso.
Principales métodos:
- Investigó las vías de señalización de Ca2+.
- Examinó la función de CREB como un factor de transcripción regulado por Ca2+.
- Se evaluó la fosforilación de CREB por las cinasas CaM in vitro e in vivo.
- Utilizó mutagénesis dirigida al sitio para alterar los sitios de fosforilación de CREB.
Principales resultados:
- CREB actúa como un factor de transcripción regulado por Ca2+.
- Las cinasas CaM I y II activadas por despolarización fosforilan CREB.
- La serina 133 (Ser133) en CREB es el sitio primario de la fosforilación mediada por la cinasa CaM.
- La mutación de Ser133 afecta significativamente la respuesta del CREB al Ca2+.
Conclusiones:
- Las quinasas CaM actúan como un conducto para las señales eléctricas al núcleo.
- CREB integra ambas vías de señalización Ca2+ y cAMP.
- La afluencia de Ca2+ después de la despolarización de la membrana es un regulador clave de la expresión génica a través de la fosforilación CREB.
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