Frizzled-9 is activated by Wnt-2 and functions in Wnt/beta -catenin signaling

J Biol Chem. 2002 Oct 4;277(40):37479-86. doi: 10.1074/jbc.M205658200. Epub 2002 Jul 22.

Abstract

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Cytosol / metabolism
  • Dishevelled Proteins
  • Frizzled Receptors
  • Gene Library
  • Genetic Vectors
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Transport
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Neurotransmitter / genetics*
  • Receptors, Neurotransmitter / metabolism
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Signal Transduction / physiology*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription, Genetic
  • Transfection
  • Wnt2 Protein
  • beta Catenin

Substances

  • Adaptor Proteins, Signal Transducing
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • DVL1 protein, human
  • Dishevelled Proteins
  • Dvl1 protein, mouse
  • Dvl1 protein, rat
  • Frizzled Receptors
  • Fzd9 protein, mouse
  • Fzd9 protein, rat
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, Neurotransmitter
  • Recombinant Proteins
  • Trans-Activators
  • Wnt2 Protein
  • beta Catenin

Associated data

  • GENBANK/AF455054