module: dmel_bmp_signaling
title: BMP signaling pathway in Drosophila melanogaster
label: BMP signaling
module_type: SIGNALING_PATHWAY
description: >-
  Bone morphogenetic protein (BMP) signaling in Drosophila is triggered by the
  ligands Decapentaplegic (Dpp), Glass bottom boat (Gbb) and Screw (Scw), which
  act as homo- or heterodimers. Ligands bind heteromeric complexes of type I
  receptor kinases (Thickveins, Saxophone) and type II receptor kinases (Punt,
  Wishful thinking). The activated type I receptor phosphorylates the
  receptor-regulated SMAD Mad, which forms a complex with the co-SMAD Medea and
  accumulates in the nucleus. With the zinc-finger protein Schnurri, the
  Mad-Medea complex represses brinker and activates other targets. The pathway
  patterns the dorsal-ventral axis of the embryo and the wing imaginal disc,
  maintains germline stem cells, and regulates synaptic growth at the
  neuromuscular junction, where Gbb and Wishful thinking act.
summary: >-
  Dpp, Gbb and Scw signal through Tkv/Sax and Punt/Wit receptors to
  phosphorylate Mad, which acts with Medea and Schnurri to regulate transcription.
concepts:
  - {id: GO:0030509, label: BMP signaling pathway}
parts:
  - id: bmp_ligands
    label: BMP ligands
    role: secreted ligands
    description: >-
      Dpp, Gbb and Scw are BMP ligands. Maverick is a divergent TGF-beta
      superfamily ligand that FlyBase includes among the core components.
    genes: [dpp, gbb, scw, mav]
    complex: false
    function: {id: GO:0005125, label: cytokine activity}
    unit_functions:
      mav: null
  - id: bmp_type_i_receptors
    label: BMP type I receptors
    role: type I receptor serine/threonine kinases
    genes: [tkv, sax]
    complex: false
    function: {id: GO:0098821, label: BMP receptor activity}
  - id: bmp_type_ii_receptors
    label: BMP type II receptors
    role: type II receptor serine/threonine kinases
    description: >-
      Punt is the main type II receptor in embryonic and imaginal BMP signaling;
      Wishful thinking acts in motor neurons at the neuromuscular junction.
    genes: [put, wit]
    complex: false
    function: {id: GO:0005026, label: "transforming growth factor beta receptor activity, type II"}
  - id: mad_medea_complex
    label: Mad-Medea SMAD complex
    role: signal transducers and transcriptional regulators
    description: Phosphorylated Mad associates with the co-SMAD Medea and enters the nucleus.
    genes: [Mad, Med]
    complex: true
    complex_term: {id: GO:0071144, label: heteromeric SMAD protein complex}
    function: {id: GO:0000981, label: "DNA-binding transcription factor activity, RNA polymerase II-specific"}
  - id: schnurri
    label: Schnurri
    role: nuclear SMAD cofactor
    description: >-
      Zinc-finger protein that joins Mad and Medea on silencer elements to
      repress brinker and other targets.
    genes: [shn]
    complex: false
connections:
  - {source: bmp_ligands, target: bmp_type_i_receptors, connection_type: POSITIVELY_REGULATES,
     description: "Ligand binding assembles type I/type II receptor complexes."}
  - {source: bmp_type_ii_receptors, target: bmp_type_i_receptors, connection_type: POSITIVELY_REGULATES,
     description: "Type II receptor kinases phosphorylate and activate the type I receptors."}
  - {source: bmp_type_i_receptors, target: mad_medea_complex, connection_type: POSITIVELY_REGULATES,
     description: "Thickveins and Saxophone phosphorylate Mad, which then associates with Medea."}
  - {source: mad_medea_complex, target: schnurri, connection_type: PROVIDES_INPUT_FOR,
     description: "Mad-Medea and Schnurri form a repressor complex on brinker silencer elements."}
notes: >-
  Boundary. Core components only (FlyBase BMP-C). Medea and the type II
  receptors Punt and Wishful thinking are shared with the activin pathway.
  Extracellular modulators (Sog, Tsg, Tolloid, Crossveinless-2) and the
  repressor Brinker are FlyBase regulators and are not parts. Maverick is kept
  in the ligand part because FlyBase lists it as core, but no receptor activity
  or ligand activity is asserted for it.