The G protein-coupled receptor GPR31 promotes membrane association of KRAS.
Nicole FehrenbacherIsrael Tojal da SilvaCraig RamirezYong ZhouKwang-Jin ChoShafi KuchayJie ShiSusan ThomasMichele PaganoJohn F HancockDafna Bar-SagiMark R PhilipsPublished in: The Journal of cell biology (2017)
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.
Keyphrases
- wild type
- genome wide
- particulate matter
- air pollution
- fatty acid
- endoplasmic reticulum
- heavy metals
- dna methylation
- gene expression
- polycyclic aromatic hydrocarbons
- machine learning
- risk assessment
- high throughput
- oxidative stress
- deep learning
- electronic health record
- artificial intelligence
- long non coding rna
- heat stress
- data analysis
- heat shock