title: An ATP-dependent activity that releases RanGDP from NTF2.
abstract: The small GTPase Ran functions in several critical processes in eukaryotic cells including nuclear transport, nuclear envelope formation, and spindle formation. A RanGDP-binding protein, NTF2, facilitates translocation of RanGDP through the nuclear pore complex and also acts to stabilize RanGDP against nucleotide exchange. Here, we identify a novel activity that stimulates release of GDP from Ran in the presence of NTF2. Hydrolyzable ATP enhances the GDP dissociation activity, and this enhancement is inhibited by nonhydrolyzable ATP analogues. In contrast, neither hydrolyzable ATP nor nonhydrolyzable ATP analogues affect GDP dissociation from Ran catalyzed by recombinant RCC1 or inhibition of GDP dissociation from Ran by recombinant NTF2. The ATP-dependent RanGDP dissociation activity therefore has the properties of a RanGDP dissociation inhibitor (GDI) displacement factor (RanGDF) where the GDI is NTF2. A protein phosphatase inhibitor mixture stimulates the RanGDF activity, suggesting the activity is regulated by phosphorylation. We propose that the ATP-dependent NTF2 releasing factor may have a role in the RanGDP/GTP cycle.
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
authors.forename: Masami
authors.initials: M
authors.lastname: Yamada
authors.forename: Iain W
authors.initials: IW
authors.lastname: Mattaj
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D021581:Active Transport, Cell Nucleus; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002384:Catalysis; D018797:Cell Cycle Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006868:Hydrolysis; D015151:Immunoblotting; D051379:Mice; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000737:chemistry; D020931:ran GTP-Binding Protein / Q000737:chemistry*
chemical_list: D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; C503613:Nutf2 protein, mouse; C499302:Rcc1 protein, mouse; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases; D020931:ran GTP-Binding Protein