title: The Nogo-B receptor promotes Ras plasma membrane localization and activation.
abstract: 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.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Key Laboratory of Separation Science, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.affiliation: Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: P
authors.initials: P
authors.lastname: Gonyo
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: U
authors.initials: U
authors.lastname: Rana
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Department of Pathology, China-Japan Friendship Hospital, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: W Q
authors.initials: WQ
authors.lastname: Duong
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Williams
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA.|Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Q R
authors.initials: QR
authors.lastname: Miao
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D066255:EGF Family of Proteins / Q000378:metabolism*; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D017368:Protein Prenylation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D066255:EGF Family of Proteins; C512615:Nogo-B receptor, mouse; D011956:Receptors, Cell Surface; D018631:ras Proteins