title: Asef is a Cdc42-specific guanine nucleotide exchange factor.
abstract: Asef is a member of the Dbl-family of guanine nucleotide exchange factors (GEFs) with a proposed specificity for the small GTPase Rac1. Here we investigated the specificity and regulation of Asef by measuring its GEF activity in vitro and observed hardly any activity towards Rac1, Rac2 and Rac3, or RhoA and TC10. In contrast, various purified Asef protein fragments catalyzed the nucleotide exchange reaction of Cdc42. The Cdc42GEF activity of the Dbl homology (DH) domain of Asef was significantly higher in the presence of the pleckstrin homology (PH) domain. Our data strongly suggest that Asef is a canonical Cdc42GEF, which employs its PH domain to efficiently stabilize its autoinhibited state, but also to facilitate nucleotide exchange activity of the DH domain after its activation by upstream signals.
authors.affiliation: Department of Structural Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, D-44227 Dortmund, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Gotthardt
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ahmadian
mesh_terms: D001665:Binding Sites; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D020033:Protein Isoforms; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein