title: Dishevelled3 is a novel arginine methyl transferase substrate.
abstract: Dishevelled, a phosphoprotein scaffold, is a central component in all the Wnt-sensitive signaling pathways. In the present study, we report that Dishevelled is post-translationally modified, both in vitro and in vivo, via arginine methylation. We also show protein arginine methyl transferases 1 and 7 as the key enzymes catalyzing Dishevelled methylation. Interestingly, Wnt3a stimulation of F9 teratocarcinoma cells results in reduced Dishevelled methylation. Similarly, the methylation-deficient mutant of Dishevelled, R271K, displayed spontaneous membrane localization and robust activation of Wnt signaling; suggesting that differential methylation of Dishevelled plays an important role in Wnt signaling. Thus arginine methylation is shown to be an important switch in regulation of Dishevelled function and Wnt signaling.
authors.affiliation: Division of Pulmonary Sciences and Critical Care, School of Medicine, Anschutz Medical Campus, University of Colorado Health Sciences Center, Aurora, Colorado 80045, USA. kamesh.bikkavilli@ucdenver.edu
authors.forename: Rama Kamesh
authors.initials: RK
authors.lastname: Bikkavilli
authors.forename: Sreedevi
authors.initials: S
authors.lastname: Avasarala
authors.forename: Michelle
authors.initials: M
authors.lastname: Vanscoyk
authors.forename: Marybeth
authors.initials: M
authors.lastname: Sechler
authors.forename: Nicole
authors.initials: N
authors.lastname: Kelley
authors.forename: Craig C
authors.initials: CC
authors.lastname: Malbon
authors.forename: Robert A
authors.initials: RA
authors.lastname: Winn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000072261:Dishevelled Proteins; D004330:Drosophila; D029721:Drosophila Proteins; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D013379:Substrate Specificity; D051153:Wnt Proteins / Q000378:metabolism; D014981:Xenopus; D015027:Zebrafish
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; C000606585:Dvl3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D051153:Wnt Proteins; C000606588:dsh protein, Drosophila; D001120:Arginine; C099988:PRMT1 protein, human; C077013:PRMT2 protein, human; C487994:PRMT7 protein, human; D011484:Protein-Arginine N-Methyltransferases