title: Conformational change of Dishevelled plays a key regulatory role in the Wnt signaling pathways.
abstract: The intracellular signaling molecule Dishevelled (Dvl) mediates canonical and non-canonical Wnt signaling via its PDZ domain. Different pathways diverge at this point by a mechanism that remains unclear. Here we show that the peptide-binding pocket of the Dvl PDZ domain can be occupied by Dvl's own highly conserved C-terminus, inducing a closed conformation. In Xenopus, Wnt-regulated convergent extension (CE) is readily affected by Dvl mutants unable to form the closed conformation than by wild-type Dvl. We also demonstrate that while Dvl cooperates with other Wnt pathway elements to activate canonical Wnt signaling, the open conformation of Dvl more effectively activates Jun N-terminal kinase (JNK). These results suggest that together with other players in the Wnt signaling pathway, the conformational change of Dvl regulates Wnt stimulated JNK activity in the non-canonical Wnt signaling.
authors: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, United States.
authors: Ho-Jin
authors: HJ
authors: Lee
authors: Laboratoire de biologie du développement, Institut de Biologie Paris-Seine, Sorbonne Universités, Paris, France.
authors: De-Li
authors: DL
authors: Shi
authors: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, United States.
authors: Jie J
authors: http://orcid.org/0000-0001-6524-6800
authors: JJ
authors: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D000072261:Dishevelled Proteins; D020935:MAP Kinase Signaling System; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D029867:Xenopus Proteins
keywords: Dishevelled; NMR; PDZ; Wnt; auto-inhibition; biophysics; cell biology; structural biology; xenopus