title: The tumor suppressor hamartin enhances Dbl protein transforming activity through interaction with ezrin.
abstract: The Rho guanine nucleotide exchange factor (GEF) Dbl binds to the N-terminal region of ezrin, a member of the ERM (ezrin, radixin, moesin) proteins known to function as linkers between the plasma membrane and the actin cytoskeleton. Here we have characterized the interaction between ezrin and Dbl. We show that binding of Dbl with ezrin involves positively charged amino acids within the region of the pleckstrin homology (PH) domain comprised between β1 and β2 sheets. In addition, we show that Dbl forms a complex with the tuberous sclerosis-1 (TSC-1) gene product hamartin and with ezrin. We demonstrate that hamartin and ezrin are both required for activation of Dbl. In fact, the knock-down of ezrin and hamartin, as well as the expression of a mutant hamartin, unable to bind ezrin, inhibit Dbl transforming and exchange activity. These results suggest that Dbl is regulated by hamartin through association with ezrin.
authors.affiliation: Laboratorio di Biologia Molecolare, Istituto G. Gaslini, Genova, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Ognibene
authors.forename: Cristina
authors.initials: C
authors.lastname: Vanni
authors.forename: Daniela
authors.initials: D
authors.lastname: Segalerba
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancini
authors.forename: Elisa
authors.initials: E
authors.lastname: Merello
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Torrisi
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Bosco
authors.forename: Luigi
authors.initials: L
authors.lastname: Varesio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Eva
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D011485:Protein Binding; D017433:Protein Structure, Secondary; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000099149:Ezrin; C512843:Mcf2 protein, mouse; C000624650:TSC1 protein, human; C000624651:Tsc1 protein, mouse