title: Distinct domains of mouse dishevelled are responsible for the c-Jun N-terminal kinase/stress-activated protein kinase activation and the axis formation in vertebrates.
abstract: Recent studies have shown that Drosophila Dishevelled (Dsh), an essential component of the wingless signal transduction, is also involved in planar polarity signaling through the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway in Drosophila. Here, we show that expression of a mouse homolog of Dsh (mDvl-1) in NIH3T3 cells activates JNK/SAPK, and its activator MKK7. A C-terminal half of mDvl-1 which contains the DEP domain was sufficient for the activation of JNK/SAPK, whereas an N-terminal half of mDvl-1 as well as the DEP domain is required for stimulation of the TCF/LEF-1-dependent transcriptional activation, a beta-catenin-dependent process. A single amino acid substitution (Met for Lys) within the DEP domain (mDvl-1 (KM)) abolished the JNK/SAPK-activating activity of mDvl-1, but did not affect the activity to activate the LEF-1-dependent transcription. Ectopic expression of mDvl-1 (KM) or an N-terminal half of mDvl-1, but not the C-terminal, was able to induce secondary axis in Xenopus embryos. Because the secondary axis formation is dependent on the Wnt/beta-catenin signaling pathway, these results suggest that distinct domains of mDvl-1 are responsible for the two downstream signaling pathways, the beta-catenin pathway and the JNK/SAPK pathway in vertebrates.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Moriguchi
authors.forename: K
authors.initials: K
authors.lastname: Kawachi
authors.forename: S
authors.initials: S
authors.lastname: Kamakura
authors.forename: N
authors.initials: N
authors.lastname: Masuyama
authors.forename: H
authors.initials: H
authors.lastname: Yamanaka
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Kikuchi
authors.forename: E
authors.initials: E
authors.lastname: Nishida
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning; D000072261:Dishevelled Proteins; D004330:Drosophila; D029721:Drosophila Proteins; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016296:Mutagenesis; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection; D014714:Vertebrates; D029867:Xenopus Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; C000606579:Dvl1 protein, mouse; D010750:Phosphoproteins; D011994:Recombinant Proteins; D029867:Xenopus Proteins; C000606588:dsh protein, Drosophila; D011494:Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; C482570:Map2k7 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases