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Estimulación hormonal de la adenilil ciclasa a través de las subunidades gamma beta de la proteína Gi

A D Federman¹, B R Conklin, K A Schrader

¹Department of Pharmacology, University of California San Francisco 94143.

|March 12, 1992

Resumen

Las subunidades beta gamma de las proteínas G inhibidoras (Gi) pueden estimular la síntesis de AMP cíclico (cAMP). Esto ocurre de manera condicional, requiriendo coestimulación por alfa s-GTP y activando la adenilil ciclasa II, revelando un nuevo papel de señalización.

Área de la Ciencia:

Biología Molecular Biología Molecular
La señalización celular de las células.
La bioquímica es la bioquímica.

Sus antecedentes:

Los receptores acoplados a proteínas G inician cascadas de señalización mediante la activación de proteínas G heterotriméricas.
Típicamente, la subunidad alfa de las proteínas G transmite señales a los efectores aguas abajo.
La evidencia emergente sugiere que las subunidades beta gamma también pueden desempeñar un papel regulador en las vías efectoras.

Objetivo del estudio:

Investigar el papel potencial de las subunidades beta gamma de la proteína G en la regulación de la actividad de la adenilil ciclasa.
Para determinar si las subunidades beta gamma de las proteínas G inhibidoras (Gi) pueden modular la síntesis de AMP cíclico (cAMP).
Para dilucidar las nuevas funciones de señalización de las subunidades Gi beta gamma en las respuestas celulares.

Principales métodos:

Coexpresión de alfa s mutantemente activo con adenilil ciclasa II en células de mamíferos.
Utilizó la toxina de la tos ferina para inactivar las proteínas Gi.
Empleó la subunidad alfa de la transducina como un recolector beta gamma.

Principales resultados:

Los agonistas que actúan a través de receptores inhibidores (acoplados a Gi) estimulan la síntesis de cAMP cuando se coexpresa con alfa s activa y adenilil ciclasa II.
La evidencia sugiere que las subunidades Gi beta gamma median esta estimulación dependiente de beta gamma de la adenilil ciclasa II.
Esta estimulación es condicional, ya que requiere tanto subunidades beta gamma como alfa s-GTP para la activación de la adenilil ciclasa II.

Conclusiones:

Las subunidades beta gamma de las proteínas Gi poseen una nueva función de señalización: estimulación condicional de la síntesis de cAMP.
Esta vía implica la activación de la adenilil ciclasa II de una manera dependiente de la alfa s-GTP.
Estos hallazgos amplían nuestra comprensión de la señalización de la proteína G más allá del papel canónico de las subunidades alfa.

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