El calcio promueve la supervivencia celular a través de la activación de la cinasa CaM-K de la vía proteína-cinasa-B
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S Yano1, H Tokumitsu, T R Soderling
1Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Nature
|December 22, 1998
Resumen
La señalización de calcio protege a las neuronas de la apoptosis mediante la activación de la proteína quinasa B (PKB) a través de la proteína quinasa quinasa Ca2+/calmodulina-dependiente (CaM-KK). Esta vía fosforila el BAD, previniendo la muerte celular programada.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los factores de crecimiento protegen a las células de la apoptosis a través de la vía PI(3)K/PKB, fosforilando BAD.
- La señalización de calcio en las neuronas puede promover la supervivencia independientemente de las quinasas PI(3) K y MAP.
- La proteína proapoptótica BAD juega un papel clave en la regulación de la muerte celular.
Objetivo del estudio:
- Para investigar el papel de la proteína kinasa kinasa Ca2+/calmodulina-dependiente (CaM-KK) en la supervivencia neuronal.
- Para dilucidar la vía de señalización que une la afluencia de calcio a la inhibición de la apoptosis.
- Para determinar si CaM-KK puede activar la proteína quinasa B (PKB) y afectar la fosforilación de BAD.
Principales métodos:
- Se utilizaron células de neuroblastoma NG108.
- Apoptosis inducida a través de la retirada de suero.
- Niveles de Ca2+ intracelulares modulados mediante el uso de NMDA o KCl.
- Transfección empleada con CaM-KK y PKB constitutivamente activos y dominantes-negativos.
- Se evaluó la muerte celular y la fosforilación de proteínas (BAD).
Principales resultados:
- La proteína kinasa kinasa dependiente de Ca2+/calmodulina (CaM-KK) activa directamente la proteína kinasa B (PKB).
- Los fosforilatos activados de PKB BAD en la serina 136, promoviendo su interacción con la proteína 14-3-3.
- El aumento de Ca2+ intracelular (a través de NMDA o KCl) o CaM-KK activo bloqueó significativamente la apoptosis inducida por la retirada del suero en las células NG108.
- La inhibición de CaM-KK o PKB eliminó los efectos neuroprotectores del NMDA.
Conclusiones:
- Una nueva cascada de señalización desencadenada por Ca2+ involucra la activación CaM-KK de PKB.
- Esta vía conduce a la fosforilación de BAD y la posterior protección contra la apoptosis.
- Este mecanismo proporciona un vínculo directo entre la señalización de calcio y la regulación de la muerte celular programada en las neuronas.
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