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Sos1 humano: un factor de intercambio de nucleótidos de guanina para Ras que se une a GRB2

P Chardin¹, J H Camonis, N W Gale

¹Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, Valbonne, France.

Science (New York, N.Y.)

|May 28, 1993

Resumen

Los investigadores identificaron hSos1, una proteína humana crucial para la señalización Ras. Actúa como un factor de intercambio de nucleótidos de guanina, interactuando con GRB2 para vincular las receptoras tirosina quinasas a las vías Ras.

Área de la Ciencia:

Biología Molecular Biología Molecular
La señalización celular de las células.
Genética La genética.

Sus antecedentes:

El gen Hijo de Sevenless (Sos) en Drosophila regula la señalización Ras.
CDC25 es un factor de intercambio de nucleótidos de guanina de levadura para Ras.
Las receptoras tirosina quinasas (RTKs) activan las vías de señalización Ras.

Objetivo del estudio:

Para identificar y caracterizar el homólogo humano de Drosophila Sos.
Para determinar la función del homólogo Sos humano (hSos1) en la señalización Ras.
Para dilucidar la interacción entre hSos1, GRB2 y RTKs.

Principales métodos:

Aislamiento y secuenciación del ADN complementario (ADNc).
Ensayos de complementación funcional en levaduras.
Ensayos de intercambio de nucleótidos de guanina in vitro.
Estudios in vivo e in vitro de interacción con las proteínas (coinmunoprecipitación).

Principales resultados:

ADNc humano aislado que codifica hSos1, una proteína ampliamente expresada.
Se demostró que un dominio de hSos1 relacionado con CDC25 complementa la función CDC25 de la levadura.
Mostrado hSos1 estimula el intercambio de nucleótidos de guanina en las proteínas Ras de los mamíferos.
Se confirmó que hSos1 interactúa con GRB2 a través de su dominio carboxilo-terminal y los dominios SH3 de GRB2.
Se observó un aumento de la actividad de intercambio de nucleótidos de guanina en las células de mamíferos que sobreexpresan hSos1.

Conclusiones:

hSos1 funciona como un factor de intercambio de nucleótidos de guanina para las proteínas Ras.
El complejo GRB2-hSos1 media el acoplamiento de las RTK a las vías de señalización Ras.

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