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Molecular and Cellular Biology, July 2003, p. 4983-4990, Vol. 23, No. 14
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.14.4983-4990.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Novel Ras Inhibitor, Eri1, Engages Yeast Ras at the Endoplasmic Reticulum {dagger}

Andrew K. Sobering,{ddagger} Martin J. Romeo, Heather A. Vay, and David E. Levin*

Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland 21205

Received 10 January 2003/ Returned for modification 3 March 2003/ Accepted 8 April 2003

Ras oncoproteins are monomeric GTPases that link signals from the cell surface to pathways that regulate cell proliferation and differentiation. Constitutively active mutant forms of Ras are found in ca. 30% of human tumors. Here we report the isolation of a novel gene from Saccharomyces cerevisiae, designated ERI1 (for endoplasmic reticulum-associated Ras inhibitor 1), which behaves genetically as an inhibitor of Ras signaling. ERI1 encodes a 68-amino-acid protein that associates in vivo with GTP-bound Ras in a manner that requires an intact Ras-effector loop, suggesting that Eri1 competes for the same binding site as Ras target proteins. We show that Eri1 localizes primarily to the membrane of the endoplasmic reticulum (ER), where it engages Ras. The recent demonstration that signaling from mammalian Ras is not restricted to the cell surface but can also proceed from the cytoplasmic face of the ER suggests a regulatory function for Eri1 at that membrane.


* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, The Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-9825. Fax: (410) 955-2926. E-mail: levin{at}jhmi.edu.

{dagger} This paper is dedicated to the memory of Ira Herskowitz, whose mentorship and support meant a great deal to D.E.L.

{ddagger} Present address: INSERM Unité 344, Endocrinologie Moléculaire, Faculté de Médecine Necker, 75730 Paris Cedex 15, France.


Molecular and Cellular Biology, July 2003, p. 4983-4990, Vol. 23, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.14.4983-4990.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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