title: Specific phosphorylation of p120-catenin regulatory domain differently modulates its binding to RhoA.
abstract: p120-catenin is an adherens junction-associated protein that controls E-cadherin function and stability. p120-catenin also binds intracellular proteins, such as the small GTPase RhoA. In this paper, we identify the p120-catenin N-terminal regulatory domain as the docking site for RhoA. Moreover, we demonstrate that the binding of RhoA to p120-catenin is tightly controlled by the Src family-dependent phosphorylation of p120-catenin on tyrosine residues. The phosphorylation induced by Src and Fyn tyrosine kinases on p120-catenin induces opposite effects on RhoA binding. Fyn, by phosphorylating a residue located in the regulatory domain of p120-catenin (Tyr112), inhibits the interaction of this protein with RhoA. By contrast, the phosphorylation of Tyr217 and Tyr228 by Src promotes a better affinity of p120-catenin towards RhoA. In agreement with these biochemical data, results obtained in cell lines support the important role of these phosphorylation sites in the regulation of RhoA activity by p120-catenin. Taken together, these observations uncover a new regulatory mechanism acting on p120-catenin that contributes to the fine-tuned regulation of the RhoA pathways during specific signaling events.
authors.affiliation: Unitat de Biofísica, Departament Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. mireia.dunach@uab.es
authors.forename: Julio
authors.initials: J
authors.lastname: Castaño
authors.forename: Guiomar
authors.initials: G
authors.lastname: Solanas
authors.forename: David
authors.initials: D
authors.lastname: Casagolda
authors.forename: Imma
authors.initials: I
authors.lastname: Raurell
authors.forename: Patricia
authors.initials: P
authors.lastname: Villagrasa
authors.forename: Xosé R
authors.initials: XR
authors.lastname: Bustelo
authors.forename: Antonio
authors.initials: A
authors.lastname: García de Herreros
authors.forename: Mireia
authors.initials: M
authors.lastname: Duñach
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017354:Point Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051177:Catenins; D015815:Cell Adhesion Molecules; C491468:Fyb protein, mouse; D010750:Phosphoproteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin