module: dmel_jak_stat_signaling
title: JAK-STAT signaling pathway in Drosophila melanogaster
label: JAK-STAT signaling
module_type: SIGNALING_PATHWAY
description: >-
  The Drosophila JAK-STAT pathway has a minimal set of core components. The
  secreted Unpaired cytokines (Upd1, Upd2, Upd3) bind the receptor Domeless,
  which is related to vertebrate gp130-type cytokine receptors. Receptor
  activation stimulates the associated Janus kinase Hopscotch, which
  phosphorylates Domeless and the single STAT, Stat92E. Phosphorylated Stat92E
  dimerizes, enters the nucleus and activates target genes. The pathway acts
  in embryonic segmentation, stem cell maintenance, hematopoiesis, intestinal
  regeneration, cellular immunity and stress responses.
summary: >-
  Unpaired cytokines activate Domeless and the JAK Hopscotch, which
  phosphorylates Stat92E to drive target gene transcription.
concepts:
  - {id: GO:0007259, label: cell surface receptor signaling pathway via JAK-STAT}
parts:
  - id: unpaired_cytokines
    label: Unpaired cytokines
    role: secreted ligands
    genes: [upd1, upd2, upd3]
    complex: false
    function: {id: GO:0048018, label: receptor ligand activity}
  - id: domeless
    label: Domeless
    role: cytokine receptor
    genes: [dome]
    complex: false
    function: {id: GO:0004896, label: cytokine receptor activity}
  - id: hopscotch
    label: Hopscotch
    role: Janus kinase
    genes: [hop]
    complex: false
    function: {id: GO:0004715, label: non-membrane spanning protein tyrosine kinase activity}
  - id: stat92e
    label: Stat92E
    role: transcription factor output
    genes: [Stat92E]
    complex: false
    function: {id: GO:0000981, label: "DNA-binding transcription factor activity, RNA polymerase II-specific"}
  - id: sarm
    label: Sarm
    role: FlyBase core component of less defined role
    description: >-
      Sarm, a TIR-domain NAD(+) hydrolase, is listed by FlyBase among the
      core components; its position in the pathway is not established.
    genes: [Sarm]
    complex: false
connections:
  - {source: unpaired_cytokines, target: domeless, connection_type: POSITIVELY_REGULATES,
     description: "Upd binding activates Domeless."}
  - {source: domeless, target: hopscotch, connection_type: POSITIVELY_REGULATES,
     description: "Receptor activation stimulates the associated JAK Hopscotch."}
  - {source: hopscotch, target: stat92e, connection_type: POSITIVELY_REGULATES,
     description: "Hopscotch phosphorylates Stat92E, which dimerizes and enters the nucleus."}
knowledge_gaps:
  - gap_statement: >-
      How Sarm contributes to JAK-STAT signaling, and at which step it acts,
      is not established.
    boundary: Core JAK-STAT signaling components.
    gap_kind: [BIOLOGY]
notes: >-
  Boundary. Core components only (FlyBase JAKSTAT-C). The decoy receptor
  Latran, Socs36E, Ptp61F, Stat92E-interacting cofactors and other FlyBase
  regulators are not parts.