Premium
The isolated catalytic hairpin of the Ras‐specific guanine nucleotide exchange factor Cdc25 Mm retains nucleotide dissociation activity but has impaired nucleotide exchange activity
Author(s) -
Sacco Elena,
Fantinato Sonia,
Manzoni Romilde,
Metalli David,
De Gioia Luca,
Fantucci Piercarlo,
Alberghina Lilia,
Vai Marco
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.11.024
Subject(s) - guanine nucleotide exchange factor , nucleotide , cdc25 , guanine , mutant , chemistry , biology , biochemistry , microbiology and biotechnology , gtpase , cell cycle , cell , gene , cyclin dependent kinase 1
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 MmT1184E , 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.