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Elementos comunes en la estimulación del factor de crecimiento y la transformación oncogénica: 85 kd actividad de

D R Kaplan, M Whitman, B Schaffhausen

|September 25, 1987

Resumen

El factor de crecimiento derivado de plaquetas (PDGF) y el antígeno T medio del polioma (MTAg) desencadenan la fosforilación de tirosina de una proteína de 85 kd, aumentando la actividad de la fosfatidilinositol (PI) quinasa. Esta fosfoproteína es un sustrato para las tirosinacinasas.

Área de la Ciencia:

Biología celular Biología celular.
Biología molecular La biología molecular.
La bioquímica es la bioquímica.

Sus antecedentes:

La fosforilación de la tirosina juega un papel crítico en las vías de señalización celular.
El factor de crecimiento derivado de plaquetas (PDGF) es un potente mitógeno involucrado en el crecimiento y la diferenciación celular.
El antígeno T medio del polioma (MTAg) es una oncoproteína viral que puede inducir la transformación celular.

Objetivo del estudio:

Investigar el papel de la fosforilación de la tirosina en las respuestas celulares a la estimulación del PDGF y la transformación de la MTAg.
Para identificar proteínas y actividades enzimáticas asociadas con estos eventos celulares.

Principales métodos:

Utilizó un anticuerpo contra la fosfotirosina (P-tyr) para la inmunoprecipitación.
Examinó la fosforilación de proteínas y la actividad de la fosfatidilinositol (PI) quinasa en las células 3T3.
Las células analizadas estimuladas por PDGF y transformadas por MTAg, v-fms, v-sis y antígeno SV40 T.

Principales resultados:

Se observó una rápida fosforilación de tirosina de una proteína de 85 kd y un aumento de la actividad de la PI quinasa tras la estimulación del PDGF o la transformación del MTAg.
La actividad de la fosfoproteína y la quinasa PI de 85 kd también se elevó en las células transformadas por v-fms y v-sis, pero no por el antígeno SV40 T.
Se encontró una fuerte correlación entre la proteína 85 kd fosforilada por tirosina y la actividad de la PI quinasa durante la purificación.

Conclusiones:

La fosfoproteína de 85 kd, probablemente una fosfatidilinositol (PI) quinasa, es un sustrato clave para el receptor PDGF y las actividades de la tirosina quinasa MTAg/pp60c-src.
Estos hallazgos aclaran una vía de señalización que involucra la fosforilación de tirosina y la activación de la PI quinasa en respuesta a los factores de crecimiento y las oncoproteínas virales.

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