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.

引用

页码：6851 / 6858

页数：8