Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/25185
Title: A T42A Ran Mutation: Differential Interactions with Effectors and Regulators, and Defect in Nuclear Protein Import
Author: Murphy, Gretchen A.
Moore, Mary Shannon
Drivas, George
Pérez de la Ossa, Pablo
Villamarin, Alicia
D'Eustachio, Peter, 1949-
Rush, Mark G., 1942-
Keywords: Proteïnes G
Trifosfatasa de guanosina
G Proteins
Guanosine triphosphatase
Issue Date: 17-Sep-1997
Publisher: American Society for Cell Biology
Abstract: Ran, the small, predominantly nuclear GTPase, has been implicated in the regulation of a variety of cellular processes including cell cycle progression, nuclear-cytoplasmic trafficking of RNA and protein, nuclear structure, and DNA synthesis. It is not known whether Ran functions directly in each process or whether many of its roles may be secondary to a direct role in only one, for example, nuclear protein import. To identify biochemical links between Ran and its functional target(s), we have generated and examined the properties of a putative Ran effector mutation, T42A-Ran. T42A-Ran binds guanine nucleotides as well as wild-type Ran and responds as well as wild-type Ran to GTP or GDP exchange stimulated by the Ran-specific guanine nucleotide exchange factor, RCC1. T42A-Ran·GDP also retains the ability to bind p10/NTF2, a component of the nuclear import pathway. In contrast to wild-type Ran, T42A-Ran·GTP binds very weakly or not detectably to three proposed Ran effectors, Ran-binding protein 1 (RanBP1), Ran-binding protein 2 (RanBP2, a nucleoporin), and karyopherin ß (a component of the nuclear protein import pathway), and is not stimulated to hydrolyze bound GTP by Ran GTPase-activating protein, RanGAP1. Also in contrast to wild-type Ran, T42A-Ran does not stimulate nuclear protein import in a digitonin permeabilized cell assay and also inhibits wild-type Ran function in this system. However, the T42A mutation does not block the docking of karyophilic substrates at the nuclear pore. These properties of T42A-Ran are consistent with its classification as an effector mutant and define the exposed region of Ran containing the mutation as a probable effector loop.
Note: Reproducció del document publicat a: http://www.molbiolcell.org/content/8/12/2591.abstract?sid=7bca83e5-9aa9-47cc-b486-a45084f72740
It is part of: Molecular Biology of the Cell, 1997, vol. 8, núm. 12, p.2591-2604
URI: http://hdl.handle.net/2445/25185
ISSN: 1059-1524
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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