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La tirosina fosfatasa CD45 es esencial para acoplar el receptor del antígeno de las células T a la vía del fosfatidil
G A Koretzky1, J Picus, M L Thomas
1Department of Medicine, University of California, San Francisco 94143.
Nature
|July 5, 1990
Resumen
La fosfatasa CD45 es crucial para la señalización del receptor de células T (TCR), lo que permite la generación de segundos mensajeros esenciales. Su ausencia bloquea la señalización de fosfatidilinositol (PtdIns) mediada por TCR, destacando el CD45.
Área de la Ciencia:
- Inmunología Inmunología.
- La señalización celular de las células.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La estimulación del receptor de células T (TCR) inicia la activación de la tirosina quinasa y el fosfatidil inositol (PtdIns) de segunda generación de mensajeros.
- CD45, una glicoproteína específica de las células hematopoyéticas con actividad de la tirosina fosfatasa, está implicada en la activación de los linfocitos.
Objetivo del estudio:
- Investigar el papel de CD45 en los eventos de transducción de señal proximal mediados por el TCR.
- Para determinar si CD45 influye en el acoplamiento del TCR a la segunda vía de mensajería de PtdIns.
Principales métodos:
- Aislamiento de una variante CD45 negativa de la línea de células T humanas HPB-ALL.
- Transfección de las células CD45 negativas con el receptor muscarínico humano tipo 1.
- Análisis de la segunda generación de mensajeros de PtdIns después de la estimulación del TCR y del receptor muscarínico.
Principales resultados:
- La estimulación de la TCR en las células CD45 negativas no logró producir segundos mensajeros derivados de PtdIns.
- La restauración de la expresión de CD45 en estas células restableció los eventos de señalización temprana mediados por TCR.
- La estimulación del receptor muscarínico de tipo 1 transfectado generó mensajeros secundarios PtdIns normales en células CD45 negativas.
Conclusiones:
- CD45 juega un papel crítico en la cascada de señalización iniciada por el TCR.
- CD45 influye en un componente celular específico esencial para acoplar el TCR a la vía PtdIns, independiente de otras vías de señalización como el receptor muscarínico.
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