Frizzled-9 is activated by Wnt-2 and functions in Wnt/beta -catenin signaling.
Frizzled has been known to function as a Wnt receptor. Although there have been a number of mammalian Frizzled members identified, their binding specificities with Wnt and functions in mammalian cells have been poorly understood. Here, we demonstrate that rat Frizzled-9 (Rfz9) functions in Wnt/beta-catenin signaling in 293T cells. Rfz9 overexpression induces the hyperphosphorylation and relocalization of mouse Dishevelled-1 (Dvl-1) from the cytoplasm to the cell membrane and the accumulation of cytosolic beta-catenin. Transfections of Rfz9 with each of several Wnt members show that only Wnt-2 activates Rfz9 in T cell factor (TCF)-dependent transcription. Deletion mutant analysis determines that there is a difference in Rfz9 C-terminal residues required for the modifications of Dvl-1 and those required for the inductions of beta-catenin stabilization and TCF transactivation. Deletion of the Wnt-binding domain does not abolish Rfz9 activity completely, although it causes the inactivation of Wnt-2-dependent TCF transcription. Rfz9 also relocalizes Axin from the cytoplasm to the plasma membrane in the presence of Dvl-1, suggesting that one of the consequences of Dvl-1 relocalization by Rfz9 is to bring Axin to the cell membrane.
Child Study Center and Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Takatoshi
T
Karasawa
Hisayuki
H
Yokokura
Jan
J
Kitajewski
Paul J
PJ
Lombroso
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors; D015723:Gene Library; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D051154:Wnt2 Protein; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; C000606578:DVL1 protein, human; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; C000606580:Dvl1 protein, rat; D051157:Frizzled Receptors; C403212:Fzd9 protein, mouse; C498590:Fzd9 protein, rat; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; D015534:Trans-Activators; D051154:Wnt2 Protein; D051176:beta Catenin