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La eliminación de SHIP o SHP-1 revela dos vías distintas para la señalización inhibidora
1Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10021, USA.
Cell
|July 25, 1997
Resumen
Los coreceptores inhibidores inmunes utilizan distintas fosfatasas, SHP-1 (SH2-que contiene inositol fosfatasa 1) o SHIP (SH2-que contiene inositol fosfatasa), para la señalización. Este reclutamiento selectivo dicta los resultados en la apoptosis desencadenada por el receptor de células B.
Área de la Ciencia:
- Inmunología Inmunología.
- La señalización celular de las células.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los coreceptores inhibidores modulan la activación de los receptores inmunes.
- El polifosfato de inositol 5'-fosfatasa (SHIP) y la tirosina fosfatasa SHP-1 son moléculas de señalización clave.
- Sus funciones específicas en las vías de señalización inhibidoras aún no se han aclarado completamente.
Objetivo del estudio:
- Investigar la necesidad, la interacción y la redundancia de SHIP y SHP-1 en la señalización inhibidora inmune.
- Para definir clases distintas de respuestas inhibidoras mediadas por estas fosfatasas.
- Para comprender su impacto en la apoptosis desencadenada por el receptor de células B (BCR).
Principales métodos:
- Generación de líneas celulares B deficientes en SHP-1 y deficientes en SHIP.
- Evaluación de las capacidades de señalización inhibidora en estas líneas celulares.
- Análisis de la apoptosis desencadenada por BCR en respuesta al compromiso del receptor.
Principales resultados:
- Se identificaron dos clases distintas de respuestas inhibidoras, reclutando selectivamente ya sea SHP-1 o SHIP.
- La señalización inhibidora mediada por Fc gammaRIIB requiere SHIP, no SHP-1.
- La señalización inhibidora mediada por KIR requiere SHP-1, no SHIP.
- La señalización SHP-1 bloquea la apoptosis, mientras que la señalización SHIP atenúa las señales proapoptóticas iniciadas por Fc gammaRIIB.
Conclusiones:
- SHIP y SHP-1 desempeñan funciones distintas y no redundantes en la mediación de la señalización inhibidora de los coreceptores.
- El reclutamiento selectivo de estas fosfatasas dicta el resultado celular, específicamente en la apoptosis desencadenada por BCR.
- Este reclutamiento selectivo proporciona un mecanismo para afinar las respuestas inmunes.
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