Nature 1997,
PMID: 9335507
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