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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
La proteína G G alfa12 estimula la tirosina quinasa de Bruton y un rasGAP a través de un dominio PH/BM conservado
1Department of Physiology, Cornell University Medical College, New York, New York 10021, USA.
Nature
|October 31, 1998
Resumen
Los investigadores descubrieron los primeros efectores directos para las proteínas G alpha12, identificando a Bruton.
Área de la Ciencia:
- Las vías de señalización celular.
- Biología molecular La biología molecular.
- Interacciones de las proteínas.
Sus antecedentes:
- Las proteínas de unión guanina-nucleótido heterotriméricas (proteínas G) son transductores de señales cruciales.
- Ellos transmiten señales extracelulares para modular los procesos intracelulares.
- Los efectores directos aguas abajo para las proteínas G alfa12 permanecieron sin identificar.
Objetivo del estudio:
- Para identificar efectores directos aguas abajo de las proteínas G alpha12.
- Para dilucidar el mecanismo de interacción entre G alpha12 y sus efectores.
- Para establecer un vínculo entre la señalización de proteínas G heterotrimérica y monomérica.
Principales métodos:
- Ensayos de unión in vitro. ensayos de unión in vitro.
- Estudios de interacción in vivo.
- Análisis de los dominios proteicos conservados.
Principales resultados:
- G alfa12 se une directamente a la tirosina quinasa de Bruton (Btk) y Gap1m.
- G alfa12 estimula la actividad de Btk y Gap1m.
- La interacción ocurre a través de un dominio conservado en Btk y Gap1m.
Conclusiones:
- La tirosina quinasa de Bruton (Btk) y Gap1m son los primeros efectores directos identificados de G alpha12.
- Se establece un vínculo directo entre las vías de señalización de la proteína G heterotrimérica (G alfa12) y la proteína G monomérica (Ras).
- Este hallazgo abre nuevas vías para comprender la transducción de señales celulares.
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