Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor biosynthesis at the ER.
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.
Sobering
Andrew K
AK
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA.
Watanabe
Reika
R
Romeo
Martin J
MJ
Yan
Benjamin C
BC
Specht
Charles A
CA
Orlean
Peter
P
Riezman
Howard
H
Levin
David E
DE
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*
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