module: dmel_sevenless_signaling
title: Sevenless receptor tyrosine kinase signaling in Drosophila melanogaster
label: Sevenless signaling pathway
module_type: SIGNALING_PATHWAY
description: >-
  Sevenless is a receptor tyrosine kinase expressed in a subset of cells of the
  developing eye that is required for the R7 photoreceptor to adopt its fate.
  It is activated by Bride of sevenless, a seven-pass transmembrane ligand on
  the neighbouring R8 cell. The activated receptor recruits the adaptor Drk
  (Grb2), the docking protein Daughter of sevenless and the tyrosine
  phosphatase Corkscrew, which together activate Son of sevenless and Ras. Ras
  drives the Raf-MEK (Dsor1)-ERK (Rolled) cascade, aided by the scaffolds Ksr
  and Cnk. ERK phosphorylates the ETS factors Pointed (activating it) and
  Yan/Aop (relieving its repression), and induces Phyllopod, which with the E3
  ligase Seven in absentia targets the repressor Tramtrack for degradation,
  allowing neuronal R7 differentiation.
summary: >-
  Boss-activated Sevenless receptor tyrosine kinase pathway that signals through
  Ras-ERK, the ETS factors Pointed and Yan, and Phyllopod-Sina degradation of
  Tramtrack to specify the R7 photoreceptor.
concepts:
  - {id: GO:0045500, label: sevenless signaling pathway}
  - {id: GO:0007465, label: R7 cell fate commitment}
parts:
  - id: boss_ligand
    label: Bride of sevenless
    role: ligand on R8
    genes: [boss]
  - id: sevenless_receptor
    label: Sevenless receptor tyrosine kinase
    role: receptor
    genes: [sev]
    function: {id: GO:0004714, label: transmembrane receptor protein tyrosine kinase activity}
  - id: sev_adaptors
    label: Receptor-proximal adaptors
    role: phosphotyrosine adaptors and docking proteins
    genes: [drk, dos, csw]
    unit_functions:
      csw: {id: GO:0004725, label: protein tyrosine phosphatase activity}
  - id: ras_activation
    label: Sos and Ras
    role: Ras activation
    genes: [Sos, Ras85D]
    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: ets_factors
    label: ETS transcription factors Pointed and Yan
    role: transcriptional output
    genes: [pnt, aop]
    unit_functions:
      pnt: {id: GO:0000981, label: "DNA-binding transcription factor activity, RNA polymerase II-specific"}
      aop: {id: GO:0001227, label: "DNA-binding transcription repressor activity, RNA polymerase II-specific"}
  - id: tramtrack_degradation
    label: Phyllopod-Sina degradation of Tramtrack
    role: removal of the neuronal repressor Tramtrack
    genes: [phyl, sina, ttk]
    unit_functions:
      sina: {id: GO:0061630, label: ubiquitin protein ligase activity}
      ttk: {id: GO:0001227, label: "DNA-binding transcription repressor activity, RNA polymerase II-specific"}
connections:
  - {source: boss_ligand, target: sevenless_receptor, connection_type: POSITIVELY_REGULATES, description: "Boss on R8 activates Sevenless on the R7 precursor."}
  - {source: sevenless_receptor, target: sev_adaptors, connection_type: POSITIVELY_REGULATES, description: "The activated receptor recruits Drk, Dos and Csw."}
  - {source: sev_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: ets_factors, connection_type: POSITIVELY_REGULATES, description: "ERK activates Pointed and inactivates Yan."}
  - {source: mapk_cascade, target: tramtrack_degradation, connection_type: POSITIVELY_REGULATES, description: "ERK signaling induces phyllopod expression, leading to Sina-mediated Tramtrack degradation."}
notes: >-
  Boundary. The Ras-ERK components are shared with other receptor tyrosine
  kinase pathways (EGFR, Torso, PVR); here they are the FlyBase Sevenless core
  components. Tramtrack is included as the substrate of the Phyllopod-Sina
  complex, as FlyBase places it among core components.