Gene interactions and pathways from curated databases and text-mining
Nature 1997, PMID: 9202126

A new protein containing an SH2 domain that inhibits JAK kinases.

Endo, T A; Masuhara, M; Yokouchi, M; Suzuki, R; Sakamoto, H; Mitsui, K; Matsumoto, A; Tanimura, S; Ohtsubo, M; Misawa, H; Miyazaki, T; Leonor, N; Taniguchi, T; Fujita, T; Kanakura, Y; Komiya, S; Yoshimura, A

The proliferation and differentiation of cells of many lineages are regulated by secreted proteins known as cytokines. Cytokines exert their biological effect through binding to cell-surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases. Cytokine-induced receptor dimerization leads to the activation of JAKs, rapid tyrosine-phosphorylation of the cytoplasmic domains, and subsequent recruitment of various signalling proteins, including members of the STAT family of transcription factors, to the receptor complex. Using the yeast two-hybrid system, we have now isolated a new SH2-domain-containing protein, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain. JAB is structurally related to CIS, a cytokine-inducible SH2 protein. Interaction of JAB with Jak1, Jak2 or Jak3 markedly reduces their tyrosine-kinase activity and suppresses the tyrosine-phosphorylation and activation of STATs. JAB and CIS appear to function as negative regulators in the JAK signalling pathway.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: SOCS1 — JAK2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SOCS1 — JAK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: SOCS1 — JAK2 (direct interaction, two hybrid)
  • IRef Hprd Interaction: SOCS1 — JAK2 (in vivo)
  • IRef Hprd Interaction: SOCS1 — JAK2 (in vitro)
  • IRef Hprd Interaction: SOCS1 — JAK2 (two hybrid)
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3/SOCS1 complex (IL2RG-JAK3-SOCS1) → IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3/SOCS1 complex (IL2RG-JAK3-SOCS1) → IL2R alpha (IL2RA) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3/SOCS1 complex (IL2RG-JAK3-SOCS1) → IL2R beta/JAK1/LCK/SOCS3 complex (IL2RB-JAK1-LCK-SOCS3) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3/SOCS1 complex (IL2RG-JAK3-SOCS1) → IL2R beta/JAK1/LCK/SOCS1 complex (IL2RB-JAK1-LCK-SOCS1) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3/SOCS1 complex (IL2RG-JAK3-SOCS1) → IL2R beta/JAK1/LCK complex (IL2RB-JAK1-LCK) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3/SOCS1 complex (IL2RG-JAK3-SOCS1) → IL2 (IL2) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3/SOCS1 complex (IL2RG-JAK3-SOCS1) → IL2R gamma/JAK3 complex (IL2RG-JAK3) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3/SOCS1 complex (IL2RG-JAK3-SOCS1) → IL2R beta/JAK1/LCK/CISH complex (IL2RB-JAK1-LCK-CISH) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3) → IL2R alpha (IL2RA) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3) → IL2R beta/JAK1/LCK complex (IL2RB-JAK1-LCK) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3) → IL2 (IL2) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3) → IL2R gamma/JAK3 complex (IL2RG-JAK3) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R alpha (IL2RA) → IL2R beta/JAK1/LCK/SOCS3 complex (IL2RB-JAK1-LCK-SOCS3) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R alpha (IL2RA) → IL2R beta/JAK1/LCK/SOCS1 complex (IL2RB-JAK1-LCK-SOCS1) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R alpha (IL2RA) → IL2R beta/JAK1/LCK complex (IL2RB-JAK1-LCK) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R alpha (IL2RA) → IL2 (IL2) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R alpha (IL2RA) → IL2R gamma/JAK3 complex (IL2RG-JAK3) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R alpha (IL2RA) → IL2R beta/JAK1/LCK/CISH complex (IL2RB-JAK1-LCK-CISH) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS3 complex (IL2RB-JAK1-LCK-SOCS3) → IL2R beta/JAK1/LCK/SOCS1 complex (IL2RB-JAK1-LCK-SOCS1) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS3 complex (IL2RB-JAK1-LCK-SOCS3) → IL2R beta/JAK1/LCK complex (IL2RB-JAK1-LCK) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS3 complex (IL2RB-JAK1-LCK-SOCS3) → IL2 (IL2) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS3 complex (IL2RB-JAK1-LCK-SOCS3) → IL2R gamma/JAK3 complex (IL2RG-JAK3) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS3 complex (IL2RB-JAK1-LCK-SOCS3) → IL2R beta/JAK1/LCK/CISH complex (IL2RB-JAK1-LCK-CISH) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS1 complex (IL2RB-JAK1-LCK-SOCS1) → IL2R beta/JAK1/LCK complex (IL2RB-JAK1-LCK) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS1 complex (IL2RB-JAK1-LCK-SOCS1) → IL2 (IL2) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS1 complex (IL2RB-JAK1-LCK-SOCS1) → IL2R gamma/JAK3 complex (IL2RG-JAK3) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK/SOCS1 complex (IL2RB-JAK1-LCK-SOCS1) → IL2R beta/JAK1/LCK/CISH complex (IL2RB-JAK1-LCK-CISH) (modification, inhibits)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK complex (IL2RB-JAK1-LCK) → IL2 (IL2) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK complex (IL2RB-JAK1-LCK) → IL2R gamma/JAK3 complex (IL2RG-JAK3) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R beta/JAK1/LCK complex (IL2RB-JAK1-LCK) → IL2R beta/JAK1/LCK/CISH complex (IL2RB-JAK1-LCK-CISH) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2 (IL2) → IL2R gamma/JAK3 complex (IL2RG-JAK3) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2 (IL2) → IL2R beta/JAK1/LCK/CISH complex (IL2RB-JAK1-LCK-CISH) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL2-mediated signaling events: IL2R gamma/JAK3 complex (IL2RG-JAK3) → IL2R beta/JAK1/LCK/CISH complex (IL2RB-JAK1-LCK-CISH) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, physical interaction, other species
  • NCI Pathway Database IL12-mediated signaling events: SOCS1 (SOCS1) → IL12/IL12R/TYK2/JAK2/SOCS1 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2-SOCS1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL12-mediated signaling events: SOCS1 (SOCS1) → IL12/IL12R/TYK2/JAK2 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL12-mediated signaling events: IL12/IL12R/TYK2/JAK2/SOCS1 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2-SOCS1) → IL12/IL12R/TYK2/JAK2 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2) (modification, collaborate)
    Evidence: physical interaction
In total, 80 gene pairs are associated to this article in curated databases