The isolated catalytic hairpin of the Ras-specific guanine nucleotide exchange factor Cdc25Mm retains nucleotide dissociation activity but has impaired nucleotide exchange activity

被引:9
作者
Sacco, E [1 ]
Fantinato, S [1 ]
Manzoni, R [1 ]
Metalli, D [1 ]
De Gioia, L [1 ]
Fantucci, P [1 ]
Alberghina, L [1 ]
Vanoni, M [1 ]
机构
[1] Univ Milan, Dipartimento Biotechnol & Biosci, I-20126 Milan, Italy
来源
FEBS LETTERS | 2005年 / 579卷 / 30期
关键词
guanine nucleotide exchange factor; Cdc25(Mm); HI hairpin; dominant negative mutants; Ras inhibitor;
D O I
10.1016/j.febslet.2005.11.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cdc25(Mm) is a mammalian Ras-specific guanine nucleotide exchange factor (GEF). By homology modeling we show that it shares with Sos-GEF the structure of the putative catalytic HI hairpin where the dominant negative T1184E mutation is located. Similarly to Cdc25(MnT1184E), the isolated wild-type and mutant hairpins retain the ability to displace Ras-bound nucleotide, originate a stable Ras/GEF complex and downregulate the Ras pathway in vivo. These results indicate that nucleotide re-entry and Ras/GEF dissociation - final steps in the GEF catalytic cycle - require GEF regions different from the HI hairpin. GEF down-sizing could lead to development of novel Ras inhibitors. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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页码:6851 / 6858
页数:8
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