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

J Cell Biol. 2017 Aug 7;216(8):2329-2338. doi: 10.1083/jcb.201609096. Epub 2017 Jun 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • A549 Cells
  • Cell Membrane / enzymology*
  • Cell Proliferation
  • Endoplasmic Reticulum / enzymology
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Mutation
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Pinocytosis
  • Prenylation
  • Protein Binding
  • Protein Isoforms
  • Protein Transport
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • RNA Interference
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Transfection
  • Tumor Burden

Substances

  • GPR31 protein, human
  • KRAS protein, human
  • Molecular Chaperones
  • Protein Isoforms
  • Receptors, G-Protein-Coupled
  • Proto-Oncogene Proteins p21(ras)