Cdc25Mm 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 Cdc25MmT1184E, 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.
Sacco, E., Fantinato, S., Manzoni, R., Metalli, D., De Gioia, L., Fantucci, P., et al. (2005). The isolated catalytic hairpin of the Ras-specific guanine nucleotide exchange factor Cdc25Mm retains nucleotide dissociation activity but has impaired nucleotide exchange activity. FEBS LETTERS, 579(30), 6851-6858 [10.1016/j.febslet.2005.11.024].
Citazione: | Sacco, E., Fantinato, S., Manzoni, R., Metalli, D., De Gioia, L., Fantucci, P., et al. (2005). The isolated catalytic hairpin of the Ras-specific guanine nucleotide exchange factor Cdc25Mm retains nucleotide dissociation activity but has impaired nucleotide exchange activity. FEBS LETTERS, 579(30), 6851-6858 [10.1016/j.febslet.2005.11.024]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Titolo: | The isolated catalytic hairpin of the Ras-specific guanine nucleotide exchange factor Cdc25Mm retains nucleotide dissociation activity but has impaired nucleotide exchange activity | |
Autori: | Sacco, E; Fantinato, S; Manzoni, R; Metalli, D; De Gioia, L; Fantucci, P; Alberghina, L; Vanoni, ME | |
Autori: | ||
Data di pubblicazione: | 19-dic-2005 | |
Lingua: | English | |
Rivista: | FEBS LETTERS | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.febslet.2005.11.024 | |
Appare nelle tipologie: | 01 - Articolo su rivista |