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Señales RAS mediadas por quinasa a través de gránulos de proteínas citoplasmáticas sin membrana

Asmin Tulpule¹, Juan Guan², Dana S Neel³

¹Division of Pediatric Hematology/Oncology, UCSF, San Francisco, CA 94143, USA.

|April 13, 2021

Resumen

Las células cancerosas utilizan nuevos gránulos de proteínas sin membrana para organizar la señalización de la tirosina quinasa receptor (RTK) y RAS / MAPK. Este descubrimiento revela una nueva vía para la señalización oncogénica independiente de las membranas lipídicas tradicionales.

Área de la Ciencia:

Biología celular
Oncología molecular
La bioquímica

Sus antecedentes:

La señalización de la receptor tirosina quinasa (RTK) generalmente ocurre en las membranas lipídicas.
La activación de la vía RAS GTPasa/MAP quinasa (MAPK) es crucial en el cáncer.

Objetivo del estudio:

Investigar plataformas subcelulares alternativas para la señalización de RTK/RAS/MAPK en el cáncer.
Identificar nuevos mecanismos de señalización oncogénica.

Principales métodos:

Análisis de las oncoproteínas quiméricas RTK (ALK, RET) en las células cancerosas.
Caracterización de la formación de gránulos de proteínas de novo.
Ensayos bioquímicos para evaluar la activación de la RAS y el conjunto del complejo de señalización.

Principales resultados:

Las oncoproteínas RTK forman gránulos de proteínas citoplasmáticas sin membrana.
Estos gránulos concentran complejos activadores del RAS (GRB2/SOS1).
La activación de RAS y la señalización de MAPK ocurren independientemente de las membranas lipídicas dentro de estos gránulos.

Conclusiones:

Los gránulos de proteína sin membrana sirven como una plataforma distinta para la señalización oncogénica de RTK y RAS.
La formación de gránulos es esencial para la salida de señales oncogénicas.
Componentes de gránulos de proteínas identificados y reglas de formación para las oncoproteínas RTK.

Palabras clave:

Cantidad total MAPK (en inglés)Las RAS RET (en inglés)Sin embargo, los pacientes con linfoma anaplásico Condensado biomolecular Fusión genética La kinasa Gránulos de proteínas Receptores de la tirosina quinasa

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