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Examination of Thymic Positive and Negative Selection by Flow Cytometry
Published on: October 8, 2012
La quinasa de señalización de estrés Sek1 protege a los timocitos de la apoptosis mediada por CD95 y CD3
H Nishina1, K D Fischer, L Radvanyi
1The Amgen Institute, Ontario Cancer Institute, Toronto, Canada.
Nature
|January 23, 1997
Resumen
Sek1 (JNKK/MKK4) es crucial para el desarrollo de las células T. La eliminación de los timocitos protegidos por Sek1 de la apoptosis, lo que indica su papel en la mediación de señales de supervivencia durante la maduración de las células T.
Área de la Ciencia:
- La señalización celular y la inmunología
- Biología molecular y genética.
Sus antecedentes:
- Las cascadas de transducción de señales controlan la supervivencia y muerte celular en respuesta a varias señales.
- Las proteínacinasas activadas por el estrés (SAPKs / JNKs) se activan por las tensiones celulares y los factores mitogénicos.
- Sek1 (JNKK/MKK4) activa directamente las SAPK/JNK, jugando un papel en las respuestas al estrés.
Objetivo del estudio:
- Investigar el papel de Sek1 en el desarrollo embrionario y la apoptosis.
- Para determinar si Sek1 es esencial para las vías de activación de SAPK/JNK.
- Aclarar la función de Sek1 en el desarrollo y supervivencia de las células T.
Principales métodos:
- Eliminación del gen sek1 en células madre embrionarias (ES) mediante recombinación homóloga.
- Generación de ratones quiméricos.
- Análisis de las poblaciones de células T (timocitos, células T maduras) y inducción de la apoptosis.
Principales resultados:
- Los ratones quiméricos exhibieron números normales de células T maduras, pero redujeron los timocitos CD4 + CD8 + inmaduros.
- La mutación de sek1 no afectó la inducción de la apoptosis en respuesta a las tensiones ambientales en las células ES y T.
- La deficiencia de Sek1 protegió a los timocitos de la apoptosis mediada por CD95 (Fas) y CD3.
Conclusiones:
- Las diferentes tensiones celulares utilizan distintas vías de señalización para la activación de SAPK/JNK.
- Sek1 no es esencial para la apoptosis inducida por el estrés, pero juega un papel crítico en el desarrollo de las células T.
- Sek1 media en señales cruciales de supervivencia durante el desarrollo de las células T, protegiendo a los timocitos de la apoptosis mediada por Fas y CD3.
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