Gene interactions and pathways from curated databases and text-mining
Nature 1997, PMID: 9335507

Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling.

Nakao, A; Afrakhte, M; Morén, A; Nakayama, T; Christian, J L; Heuchel, R; Itoh, S; Kawabata, M; Heldin, N E; Heldin, C H; ten Dijke, P

TGF-beta signals from the membrane to the nucleus through serine/threonine kinase receptors and their downstream effectors, termed SMAD proteins. The activated TGF-beta receptor induces phosphorylation of two such proteins, Smad2 and Smad3, which form hetero-oligomeric complex(es) with Smad4/DPC4 that translocate to the nucleus, where they then regulate transcriptional responses. However, the mechanisms by which the intracellular signals of TGF-beta are switched off are unclear. Here we report the identification of Smad7, which is related to Smad6. Transfection of Smad7 blocks responses mediated by TGF-beta in mammalian cells, and injection of Smad7 RNA into Xenopus embryos blocks activin/TGF-beta signalling. Smad7 associates stably with the TGF-beta receptor complex, but is not phosphorylated upon TGF-beta stimulation. TGFbeta-mediated phosphorylation of Smad2 and Smad3 is inhibited by Smad7, indicating that the antagonistic effect of Smad7 is exerted at this important regulatory step. TGF-beta rapidly induces expression of Smad7 mRNA, suggesting that Smad7 may participate in a negative feedback loop to control TGF-beta responses.

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Text Mining Data

Smad2 ⊣ Smad7: " TGFbeta mediated phosphorylation of Smad2 and Smad3 is inhibited by Smad7 , indicating that the antagonistic effect of Smad7 is exerted at this important regulatory step "

Smad3 ⊣ Smad7: " TGFbeta mediated phosphorylation of Smad2 and Smad3 is inhibited by Smad7 , indicating that the antagonistic effect of Smad7 is exerted at this important regulatory step "

Manually curated Databases

  • IRef Biogrid Interaction: SMAD7 — TGFBR2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SMAD7 — TGFBR1 (physical association, affinity chromatography technology)
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) → TGFB/TGFBR2/TGFBR1/STRAP/SMAD7 complex (TGFBR1-STRAP-SMAD7-TGFBR2) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7 (SMAD7) → TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7 (SMAD7) → TGFB/TGFBR2/TGFBR1/STRAP/SMAD7 complex (TGFBR1-STRAP-SMAD7-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7 (SMAD7) → TGFB/TGFBR2/TGFBR1/STRAP complex (TGFBR1-STRAP-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) → TGFB/TGFBR2/TGFBR1/STRAP/SMAD7 complex (TGFBR1-STRAP-SMAD7-TGFBR2) (modification, inhibits)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) → TGFB/TGFBR2/TGFBR1/STRAP complex (TGFBR1-STRAP-TGFBR2) (modification, inhibits)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/STRAP/SMAD7 complex (TGFBR1-STRAP-SMAD7-TGFBR2) → TGFB/TGFBR2/TGFBR1/STRAP complex (TGFBR1-STRAP-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7/SMURF1-2 complex (SMAD7-SMURF1_SMURF2) → TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7/SMURF1-2 complex (SMAD7-SMURF1_SMURF2) → TGFB/TGFBR2/TGFBR1 complex (TGFBR1-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7/SMURF1-2 complex (SMAD7-SMURF1_SMURF2) → Caveolin-1 (CAV1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7/SMURF1-2 complex (SMAD7-SMURF1_SMURF2) → TGFB/TGFBR2/TGFBR1/SMAD7/SMURF1-2/CAV1 complex (TGFBR1-SMAD7-SMURF1_SMURF2-CAV1-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7/SMURF1-2 complex (SMAD7-SMURF1_SMURF2) → PML/SARA/SMAD2-3 complex (ZFYVE9-SMAD2_SMAD3-PML) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: SMAD7/SMURF1-2 complex (SMAD7-SMURF1_SMURF2) → FKBP12 (FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) → TGFB/TGFBR2/TGFBR1 complex (TGFBR1-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) → Caveolin-1 (CAV1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) → TGFB/TGFBR2/TGFBR1/SMAD7/SMURF1-2/CAV1 complex (TGFBR1-SMAD7-SMURF1_SMURF2-CAV1-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) → PML/SARA/SMAD2-3 complex (ZFYVE9-SMAD2_SMAD3-PML) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1 complex (TGFBR1-TGFBR2) → Caveolin-1 (CAV1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1 complex (TGFBR1-TGFBR2) → TGFB/TGFBR2/TGFBR1/SMAD7/SMURF1-2/CAV1 complex (TGFBR1-SMAD7-SMURF1_SMURF2-CAV1-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1 complex (TGFBR1-TGFBR2) → PML/SARA/SMAD2-3 complex (ZFYVE9-SMAD2_SMAD3-PML) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1 complex (TGFBR1-TGFBR2) → FKBP12 (FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: Caveolin-1 (CAV1) → TGFB/TGFBR2/TGFBR1/SMAD7/SMURF1-2/CAV1 complex (TGFBR1-SMAD7-SMURF1_SMURF2-CAV1-TGFBR2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: Caveolin-1 (CAV1) → PML/SARA/SMAD2-3 complex (ZFYVE9-SMAD2_SMAD3-PML) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: Caveolin-1 (CAV1) → FKBP12 (FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/SMAD7/SMURF1-2/CAV1 complex (TGFBR1-SMAD7-SMURF1_SMURF2-CAV1-TGFBR2) → PML/SARA/SMAD2-3 complex (ZFYVE9-SMAD2_SMAD3-PML) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: PML/SARA/SMAD2-3 complex (ZFYVE9-SMAD2_SMAD3-PML) → FKBP12 (FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database TGF-beta receptor signaling: TGFB/TGFBR2/TGFBR1/PML/SARA/SMAD2-3/AP2B2 complex (TGFBR1-PML-ZFYVE9-SMAD2_SMAD3-TGFBR2) → TGFB/TGFBR2/TGFBR1/STRAP/SMAD7 complex (TGFBR1-STRAP-SMAD7-TGFBR2) (modification, activates)
    Evidence: mutant phenotype, physical interaction
  • Reactome Reaction: TGFB1 → TGFBR1 (indirect_complex)
  • Reactome Reaction: SMAD7 → TGFB1 (indirect_complex)
  • Reactome Reaction: TGFBR1 → TGFBR2 (indirect_complex)
  • Reactome Reaction: TGFB1 → TGFBR2 (indirect_complex)
  • Reactome Reaction: SMAD7 → TGFBR1 (reaction)
  • Reactome Reaction: SMAD7 → TGFBR2 (reaction)
  • Reactome Reaction: SMAD7 → TGFBR1 (indirect_complex)
  • Reactome Reaction: SMAD7 → TGFBR2 (indirect_complex)
  • Reactome Reaction: SMAD7 → TGFB1 (reaction)
In total, 76 gene pairs are associated to this article in curated databases