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Proliferación celular inducida por lisofosfatidato: identificación y disección de vías de señalización mediadas por

E J van Corven¹, A Groenink, K Jalink

¹Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.

|October 6, 1989

Resumen

El ácido lisofosfatídico (LPA) estimula la proliferación de fibroblastos a través de una vía sensible a las toxinas de la tos ferina que involucra a la proteína Gi. Esta señalización es distinta de las vías que activan la proteína quinasa C, lo que sugiere un nuevo papel para el LPA en la señalización de la proteína G.

Área de la Ciencia:

Biología celular Biología celular.
La bioquímica es la bioquímica.
Transducción de señales Transducción de señales.

Sus antecedentes:

El ácido lisofosfatídico (LPA) es un fosfolípido simple conocido por ser mitogénico para los fibroblastos quiescentes.
La proliferación celular inducida por LPA es independiente de otros mitógenos y es sensible a la toxina de la tos ferina.

Objetivo del estudio:

Para dilucidar las vías de señalización específicas que median la mitogénesis inducida por LPA en los fibroblastos.
Diferenciar las funciones de varias vías acopladas a proteínas G activadas por LPA.

Principales métodos:

Tratamiento de la toxina de la tos ferina para evaluar la participación de la proteína Gi.
Medición de la hidrólisis del fosfoinosituro y la movilización de Ca2+.
Análisis de la liberación de ácido araquidónico.
Evaluación de la actividad de la adenilato ciclasa.
Comparación con la señalización de la bradicinina.

Principales resultados:

La LPA activa al menos tres cascadas de señalización distintas: la hidrólisis de los fosfoinosítidos (insensibles a la toxina de la tos ferina), la liberación de ácido araquidónico (dependiente de GTP) y la inhibición de la adenilato ciclasa (proteína Gi sensible a la toxina de la tos ferina).
La bradicinina imita las dos primeras respuestas de LPA, pero no activa Gi ni estimula la síntesis de ADN.
La vía de hidrólisis-proteína quinasa C del fosfoinosítido no es esencial para la mitogénesis inducida por LPA.

Conclusiones:

La mitogénesis inducida por LPA en los fibroblastos está mediada principalmente por la vía de la proteína Gi sensible a la toxina de la tos ferina.
La vía de hidrólisis de los fosfoinosítidos no es necesaria ni suficiente para la proliferación celular impulsada por LPA.
El LPA y los fosfolípidos relacionados pueden desempeñar un papel novedoso en la transducción de señales mediada por proteínas G.

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