2. Academic Validation
  3. The G protein-coupled receptor GPR31 promotes membrane association of KRAS

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.
Nicole Fehrenbacher 1,  Israel Tojal da Silva 2,  Craig Ramirez 3,  Yong Zhou 4,  Kwang-Jin Cho 4,  Shafi Kuchay 3 5 6,  Jie Shi 3,  Susan Thomas 3,  Michele Pagano 3 5 6,  John F Hancock 4,  Dafna Bar-Sagi 3,  Mark R Philips 7
Affiliations

Affiliations

  • 1 Perlmutter Cancer Center, New York University School of Medicine, New York, NY nfehren01@gmail.com.
  • 2 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.
  • 3 Perlmutter Cancer Center, New York University School of Medicine, New York, NY.
  • 4 Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston, Houston, TX.
  • 5 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY.
  • 6 Howard Hughes Medical Institute, New York, NY.
  • 7 Perlmutter Cancer Center, New York University School of Medicine, New York, NY philim01@nyumc.org.
PMID: 28619714 DOI: 10.1083/jcb.201609096
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.

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