Gene interactions and pathways from curated databases and text-mining
Blood 1998, PMID: 9516124

JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation.

Ogata, N; Kouro, T; Yamada, A; Koike, M; Hanai, N; Ishikawa, T; Takatsu, K

The human interleukin-5 receptor (hIL-5R) consists of a unique alpha subunit (hIL-5Ralpha) and a common beta subunit (betac) that activate two Janus kinases (JAK1 and JAK2) and a signal transducer and activator of transcription (STAT5). The precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in IL-5 signaling were investigated. We analyzed the interaction between hIL-5Ralpha and betac by immunoprecipitation using anti-hIL-5Ralpha and anti-betac monoclonal antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated in the hIL-5-responsive cell line, TF-h5Ralpha. It was observed that IL-5 stimulation induced the recruitment of betac to hIL-5Ralpha, although in the absence of IL-5 the subunits remain independent. In the absence of IL-5, JAK2 and JAK1 were associated with hIL-5Ralpha and betac, respectively. IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1, betac, and STAT5. Moreover, IL-5-induced dimerization of IL-5R subunits caused JAK2 activation and betac phosphorylation even in the absence of JAK1 activation. Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2. Detailed study of the C-terminal truncated cytoplasmic domain of hIL-5Ralpha revealed that the cytoplasmic stretch at position 346-387, containing the proline-rich region, is necessary for JAK2 binding. These observations suggest that activation of hIL-5Ralpha-associated JAK2 is indispensable for the IL-5 signaling event.

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Text Mining Data

STAT5 ⊣ IL-5: " IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1, betac, and STAT5 "

JAK1 ⊣ IL-5: " IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1 , betac, and STAT5 "

JAK1 → IL-5: " IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1 , betac, and STAT5 "

JAK1 → JAK2: " Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2 "

Manually curated Databases

  • IRef Biogrid Interaction: JAK1 — IL5RA (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: JAK2 — IL5RA (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: JAK2 — IL5RA (direct interaction, pull down)
  • IRef Biogrid Interaction: CSF2RB — IL5RA (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: JAK2 — JAK2 (in vivo)
  • IRef Hprd Interaction: JAK2 — JAK2 (in vitro)
  • IRef Hprd Interaction: JAK1 — IL5RA (in vitro)
  • IRef Hprd Interaction: IL5RA — JAK2 (in vitro)
  • IRef Hprd Interaction: IL5RA — JAK2 (in vivo)
  • IRef Hprd Interaction: CSF2RB — IL5RA (in vivo)
  • IRef Ophid Interaction: IL5RA — JAK2 (aggregation, confirmational text mining)
  • NCI Pathway Database IL5-mediated signaling events: IL5 (IL5) → IL5/IL5RA/JAK2 complex (IL5RA-JAK2-IL5) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL5-mediated signaling events: IL5 (IL5) → IL5RA/JAK2 complex (IL5RA-JAK2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL5-mediated signaling events: IL5/IL5RA/JAK2 complex (IL5RA-JAK2-IL5) → IL5RA/JAK2 complex (IL5RA-JAK2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL5-mediated signaling events: IL5/IL5RA/JAK2 complex (IL5RA-JAK2-IL5) → IL5/IL5RA/CSF2RB (hexamer)/JAK2/JAK2 complex (CSF2RB-IL5-IL5RA-JAK2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL5-mediated signaling events: IL5/IL5RA/JAK2 complex (IL5RA-JAK2-IL5) → CSF2RB (dimer) complex (CSF2RB) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL5-mediated signaling events: IL5/IL5RA/CSF2RB (hexamer)/JAK2/JAK2 complex (CSF2RB-IL5-IL5RA-JAK2) → CSF2RB (dimer) complex (CSF2RB) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 11 gene pairs are associated to this article in curated databases