The Nogo-B receptor promotes Ras plasma membrane localization and activation. Oncogene 2017 Jun 15;36(24):3406-3416
Date
01/10/2017Pubmed ID
28068323Pubmed Central ID
PMC5472485DOI
10.1038/onc.2016.484Scopus ID
2-s2.0-85008618992 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
The localization of prenylated Ras at the plasma membrane promotes activation of Ras by receptor tyrosine kinases and stimulates oncogenic signaling by mutant Ras. The Nogo-B receptor (NgBR) is a transmembrane receptor that contains a conserved hydrophobic pocket. Here, we demonstrate that the NgBR promotes the membrane accumulation of Ras by directly binding prenylated Ras at the plasma membrane. We show that NgBR knockdown diminishes the membrane localization of Ras in multiple cell types. NgBR overexpression in NIH-3T3 fibroblasts increases membrane-associated Ras, induces the transformed phenotype in vitro, and promotes the formation of fibrosarcoma in nude mice. NgBR knockdown in human breast cancer cells reduces Ras membrane localization, inhibits epidermal growth factor (EGF)-stimulated Ras signaling and diminishes tumorigenesis of xenografts in nude mice. Our data demonstrate that NgBR is a unique receptor that promotes accumulation of prenylated Ras at the plasma membrane and promotes EGF pathways.
Author List
Zhao B, Hu W, Kumar S, Gonyo P, Rana U, Liu Z, Wang B, Duong WQ, Yang Z, Williams CL, Miao QRAuthors
Suresh Kumar PhD Associate Professor in the Pathology department at Medical College of WisconsinCarol L. Williams PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBreast Neoplasms
Cell Line, Tumor
Cell Membrane
EGF Family of Proteins
Female
Fibrosarcoma
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Mice
Mice, Nude
NIH 3T3 Cells
Neoplasm Transplantation
Protein Prenylation
Receptors, Cell Surface
Signal Transduction
ras Proteins
