module: dmel_torso_signaling
title: Torso receptor tyrosine kinase signaling in Drosophila melanogaster
label: Torso signaling pathway
module_type: SIGNALING_PATHWAY
description: >-
  Torso is a receptor tyrosine kinase that is uniformly distributed in the
  early embryo membrane but activated only at the anterior and posterior poles,
  where it specifies the terminal structures. Local activation depends on
  Torso-like, which is deposited at the poles by follicle cells and acts
  together with eggshell components (Nasrat/fs(1)N, Polehole/fs(1)M3 and
  Closca) to allow activation of Torso by its ligand Trunk. Torso signals
  through Drk, Sos and Ras to the Raf-MEK (Dsor1)-ERK (Rolled) cascade.
  ERK phosphorylation relieves repression by Capicua, which with the
  corepressor Groucho represses the terminal gap genes tailless and huckebein
  outside the poles. In the larval prothoracic gland, Torso is activated by
  prothoracicotropic hormone (PTTH) to trigger ecdysone production and the
  onset of metamorphosis.
summary: >-
  Receptor tyrosine kinase pathway in which Trunk (embryo) or PTTH (prothoracic
  gland) activate Torso and Ras-ERK, relieving Capicua repression.
concepts:
  - {id: GO:0008293, label: torso signaling pathway}
  - {id: GO:0007362, label: terminal region determination}
parts:
  - id: terminal_eggshell_factors
    label: Torso-like and eggshell factors
    role: localized activation at the embryo poles
    description: >-
      Torso-like is secreted by terminal follicle cells; Nasrat, Polehole and
      Closca are vitelline membrane-associated proteins required for terminal
      signaling.
    genes: [tsl, fs(1)N, fs(1)M3, clos]
  - id: torso_ligands
    label: Torso ligands
    role: ligands
    variant_sets:
      - id: torso_ligand_variants
        label: Trunk or PTTH
        selection: ONE_OR_MORE
        variants:
          - {id: trunk_ligand, label: Trunk in the early embryo, genes: [trk]}
          - {id: ptth_ligand, label: PTTH in the prothoracic gland, genes: [Ptth]}
  - id: torso_receptor
    label: Torso receptor tyrosine kinase
    role: receptor
    genes: [tor]
    function: {id: GO:0004714, label: transmembrane receptor protein tyrosine kinase activity}
  - id: torso_adaptors
    label: Receptor-proximal adaptors
    role: phosphotyrosine adaptors and docking proteins
    genes: [drk, dos, csw, Shc]
    unit_functions:
      csw: {id: GO:0004725, label: protein tyrosine phosphatase activity}
  - id: ras_activation
    label: Sos, Ras and Rap1
    role: small GTPase activation
    genes: [Sos, Ras85D, Rap1]
    unit_functions:
      Sos: {id: GO:0005085, label: guanyl-nucleotide exchange factor activity}
      Ras85D: {id: GO:0003924, label: GTPase activity}
  - id: mapk_cascade
    label: Raf-MEK-ERK cascade with scaffolds
    role: MAPK cascade
    genes: [Raf, ksr, cnk, Dsor1, rl]
    unit_functions:
      Raf: {id: GO:0004709, label: MAP kinase kinase kinase activity}
      Dsor1: {id: GO:0004708, label: MAP kinase kinase activity}
      rl: {id: GO:0004707, label: MAP kinase activity}
    processes:
      - {id: GO:0000165, label: MAPK cascade}
  - id: transcriptional_output
    label: Capicua-Groucho repression and Bicoid
    role: transcriptional output
    description: >-
      Capicua and Groucho repress terminal genes outside the poles; ERK
      signaling relieves this repression. Bicoid, the anterior morphogen, is
      a FlyBase core member because Torso signaling modulates its activity at
      the anterior pole.
    genes: [cic, gro, bcd]
    unit_functions:
      cic: {id: GO:0001227, label: "DNA-binding transcription repressor activity, RNA polymerase II-specific"}
      gro: {id: GO:0003714, label: transcription corepressor activity}
      bcd: {id: GO:0000981, label: "DNA-binding transcription factor activity, RNA polymerase II-specific"}
connections:
  - {source: terminal_eggshell_factors, target: torso_ligands, connection_type: POSITIVELY_REGULATES, description: "Torso-like and eggshell factors allow local production of active Trunk at the poles."}
  - {source: torso_ligands, target: torso_receptor, connection_type: POSITIVELY_REGULATES, description: "Trunk or PTTH activates Torso."}
  - {source: torso_receptor, target: torso_adaptors, connection_type: POSITIVELY_REGULATES, description: "The activated receptor recruits phosphotyrosine adaptors."}
  - {source: torso_adaptors, target: ras_activation, connection_type: POSITIVELY_REGULATES, description: "Drk recruits Sos, which activates Ras."}
  - {source: ras_activation, target: mapk_cascade, connection_type: POSITIVELY_REGULATES, description: "Ras-GTP activates Raf."}
  - {source: mapk_cascade, target: transcriptional_output, connection_type: NEGATIVELY_REGULATES, description: "ERK relieves Capicua-mediated repression of terminal genes."}
notes: >-
  Boundary. The Ras-ERK components are shared with other receptor tyrosine
  kinase pathways. The connection from MAPK cascade to transcriptional output
  is negative because ERK inactivates the repressor Capicua; Bicoid sits in
  the same part only because FlyBase lists it among core components. Rap1 is a
  FlyBase core member; its role relative to Ras in Torso signaling is less
  clear.