module: dmel_wnt_tcf_signaling
title: Wnt-TCF (canonical Wingless) signaling in Drosophila melanogaster
label: Wnt-TCF signaling pathway
module_type: SIGNALING_PATHWAY
description: >-
  In canonical Wnt signaling, secreted Wnt proteins, chiefly Wingless, bind
  Frizzled receptors and the LRP5/6 co-receptor Arrow. Wnt secretion requires
  palmitoleoylation by Porcupine and transport by Wntless. In the absence of
  ligand, a destruction complex of Axin, Adenomatous polyposis coli (Apc or
  Apc2), Casein kinase I alpha and Shaggy (GSK3) phosphorylates Armadillo
  (beta-catenin) and targets it for degradation. Ligand engagement recruits
  Dishevelled and Axin to the receptor, inhibiting the destruction complex, so
  that Armadillo accumulates, enters the nucleus and joins Pangolin (TCF),
  Legless (BCL9), Pygopus, Chip and Ssdp in a Wnt enhanceosome that activates
  Wingless target genes. The pathway patterns the embryonic segments, the wing,
  and many other tissues.
summary: >-
  Wingless/Wnt binding to Frizzled and Arrow inhibits the Axin-APC destruction
  complex, stabilizing Armadillo, which activates targets with Pangolin/TCF in
  the Wnt enhanceosome.
concepts:
  - {id: GO:0060070, label: canonical Wnt signaling pathway}
parts:
  - id: wnt_production
    label: Wnt production
    role: ligand acylation and secretion
    group: WNT-PRO
    unit_functions:
      por: {id: GO:1990698, label: palmitoleoyltransferase activity}
    processes:
      - {id: GO:0061355, label: Wnt protein secretion}
  - id: wnt_ligands
    label: Wnt ligands
    role: ligands
    genes: [wg, Wnt2, Wnt6, Wnt10]
    function: {id: GO:0005109, label: frizzled binding}
  - id: wnt_receptors
    label: Frizzled receptors and Arrow co-receptor
    role: receptors
    genes: [fz, fz2, arr]
    unit_functions:
      fz: {id: GO:0042813, label: Wnt receptor activity}
      fz2: {id: GO:0042813, label: Wnt receptor activity}
  - id: dishevelled
    label: Dishevelled
    role: cytoplasmic transducer
    genes: [dsh]
  - id: destruction_complex
    label: Beta-catenin destruction complex
    role: Armadillo phosphorylation and degradation
    variant_sets:
      - id: destruction_complex_variants
        label: Apc or Apc2 destruction complex
        selection: ONE_OR_MORE
        variants:
          - id: destruction_complex_apc
            label: Destruction complex, Apc variant
            group: DES-C
            complex: true
            complex_term: {id: GO:0030877, label: beta-catenin destruction complex}
            unit_functions:
              sgg: {id: GO:0004674, label: protein serine/threonine kinase activity}
              CkIalpha: {id: GO:0004674, label: protein serine/threonine kinase activity}
          - id: destruction_complex_apc2
            label: Destruction complex, Apc2 variant
            group: DES-C2
            complex: true
            complex_term: {id: GO:0030877, label: beta-catenin destruction complex}
            unit_functions:
              sgg: {id: GO:0004674, label: protein serine/threonine kinase activity}
              CkIalpha: {id: GO:0004674, label: protein serine/threonine kinase activity}
  - id: wnt_enhanceosome
    label: Wnt enhanceosome
    role: nuclear transcriptional output
    description: >-
      Armadillo bound to Pangolin on Wnt response elements, with the adaptor
      Legless, Pygopus, and the Chip-Ssdp complex.
    complex: true
    group: WNT-E
    unit_functions:
      pan: {id: GO:0000981, label: "DNA-binding transcription factor activity, RNA polymerase II-specific"}
      arm: {id: GO:0003713, label: transcription coactivator activity}
connections:
  - {source: wnt_production, target: wnt_ligands, connection_type: POSITIVELY_REGULATES, description: "Porcupine and Wntless are required for Wnt acylation and secretion."}
  - {source: wnt_ligands, target: wnt_receptors, connection_type: POSITIVELY_REGULATES, description: "Wnt binds Frizzled and Arrow."}
  - {source: wnt_receptors, target: dishevelled, connection_type: POSITIVELY_REGULATES, description: "The ligand-bound receptor recruits Dishevelled."}
  - {source: dishevelled, target: destruction_complex, connection_type: NEGATIVELY_REGULATES, description: "Dishevelled and receptor recruitment of Axin inhibit the destruction complex."}
  - {source: destruction_complex, target: wnt_enhanceosome, connection_type: NEGATIVELY_REGULATES, description: "The destruction complex targets Armadillo for degradation, preventing enhanceosome activation."}
notes: >-
  Boundary. The module combines the FlyBase Wnt-TCF pathway core, Wnt
  production, the Wnt enhanceosome and the two destruction complex variants.
  Armadillo, Pangolin, Legless and Pygopus are FlyBase core components and also
  enhanceosome members; they are modelled once, in the enhanceosome. Axin,
  Shaggy and Casein kinase I alpha are shared by both destruction complex
  variants. The SCF-Slimb ubiquitin ligase that degrades phosphorylated
  Armadillo, the corepressor Groucho and other modulators are FlyBase regulator
  sets and not parts. Arrow has no molecular function assigned because the GO
  term for Wnt coreceptor activity is obsolete.