The G protein–coupled receptor GPR31 promotes membrane association of KRAS

The product of the KRAS oncogene, KRAS4B, promotes tumor growth when associated with the plasma membrane (PM). PM association is mediated, in part, by farnesylation of KRAS4B, but trafficking of nascent KRAS4B to the PM is incompletely understood. We performed a genome-wide screen to identify genes...

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Detalles Bibliográficos
Autores principales: Fehrenbacher, Nicole, Tojal da Silva, Israel, Ramirez, Craig, Zhou, Yong, Cho, Kwang-Jin, Kuchay, Shafi, Shi, Jie, Thomas, Susan, Pagano, Michele, Hancock, John F., Bar-Sagi, Dafna, Philips, Mark R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551702/
https://www.ncbi.nlm.nih.gov/pubmed/28619714
http://dx.doi.org/10.1083/jcb.201609096
Descripción
Sumario:The product of the KRAS oncogene, KRAS4B, promotes tumor growth when associated with the plasma membrane (PM). PM association is mediated, in part, by farnesylation of KRAS4B, but trafficking of nascent KRAS4B to the PM is incompletely understood. We performed a genome-wide screen to identify genes required for KRAS4B membrane association and identified a G protein–coupled receptor, GPR31. GPR31 associated with KRAS4B on cellular membranes in a farnesylation-dependent fashion, and retention of GPR31 on the endoplasmic reticulum inhibited delivery of KRAS4B to the PM. Silencing of GPR31 expression partially mislocalized KRAS4B, slowed the growth of KRAS-dependent tumor cells, and blocked KRAS-stimulated macropinocytosis. Our data suggest that GPR31 acts as a secretory pathway chaperone for KRAS4B.

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