title: Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor biosynthesis at the ER.
abstract: The yeast ERI1 gene encodes a small ER-localized protein that associates in vivo with GTP bound Ras2 in an effector loop-dependent manner. We showed previously that loss of Eri1 function results in hyperactive Ras phenotypes. Here, we demonstrate that Eri1 is a component of the GPI-GlcNAc transferase (GPI-GnT) complex in the ER, which catalyzes transfer of GlcNAc from UDP-GlcNAc to an acceptor phosphatidylinositol, the first step in the production of GPI-anchors for cell surface proteins. We also show that GTP bound Ras2 associates with the GPI-GnT complex in vivo and inhibits its activity, indicating that yeast Ras uses the ER as a signaling platform from which to negatively regulate the GPI-GnT. We propose that diminished GPI-anchor protein production contributes to hyperactive Ras phenotypes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sobering
authors.forename: Reika
authors.initials: R
authors.lastname: Watanabe
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Romeo
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Yan
authors.forename: Charles A
authors.initials: CA
authors.lastname: Specht
authors.forename: Peter
authors.initials: P
authors.lastname: Orlean
authors.forename: Howard
authors.initials: H
authors.lastname: Riezman
authors.forename: David E
authors.initials: DE
authors.lastname: Levin
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D002686:Chitin / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C476124:Eri1 protein, S cerevisiae; C102317:GPI1 protein, S cerevisiae; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D002686:Chitin; D014537:Uridine Diphosphate N-Acetylglucosamine; D006160:Guanosine Triphosphate; D018631:ras Proteins