Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor biosynthesis at the ER

Andrew K. Sobering; Reika Watanabe; Martin J. Romeo; Benjamin C. Yan; Charles A. Specht; Peter Orlean; Howard Riezman; David E. Levin

doi:10.1016/j.cell.2004.05.003

Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor biosynthesis at the ER

Andrew K. Sobering, Reika Watanabe, Martin J. Romeo, Benjamin C. Yan, Charles A. Specht, Peter Orlean, Howard Riezman, David E. Levin

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

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.

Original language	English (US)
Pages (from-to)	637-648
Number of pages	12
Journal	Cell
Volume	117
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2004.05.003
State	Published - May 28 2004
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2004.05.003

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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.",

author = "Sobering, {Andrew K.} and Reika Watanabe and Romeo, {Martin J.} and Yan, {Benjamin C.} and Specht, {Charles A.} and Peter Orlean and Howard Riezman and Levin, {David E.}",

note = "Funding Information: We thank V. Culotta for the gas1Δ strain; S. Powers, R. Deschenes and K. Lee for Ras strains and plasmids; and L. Popolo for anti-Gas1 serum. We also thank M. Show and G. Wartzmann for assistance with the high copy suppressor screen and construction of the GFA1 reporter. This work was supported by NIH grants GM48533, GM67698 (DEL), and GM46220 (PO), a Human Frontiers Science Program Organization grant (HR) and long-term fellowship (RW), a Swiss National Science Foundation grant (HR), and NCI training grant 5T32CA09110.",

year = "2004",

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language = "English (US)",

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AU - Sobering, Andrew K.

AU - Watanabe, Reika

AU - Romeo, Martin J.

AU - Yan, Benjamin C.

AU - Specht, Charles A.

AU - Orlean, Peter

AU - Riezman, Howard

AU - Levin, David E.

N1 - Funding Information: We thank V. Culotta for the gas1Δ strain; S. Powers, R. Deschenes and K. Lee for Ras strains and plasmids; and L. Popolo for anti-Gas1 serum. We also thank M. Show and G. Wartzmann for assistance with the high copy suppressor screen and construction of the GFA1 reporter. This work was supported by NIH grants GM48533, GM67698 (DEL), and GM46220 (PO), a Human Frontiers Science Program Organization grant (HR) and long-term fellowship (RW), a Swiss National Science Foundation grant (HR), and NCI training grant 5T32CA09110.

PY - 2004/5/28

Y1 - 2004/5/28

N2 - 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.

AB - 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.

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Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor biosynthesis at the ER

Abstract

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