Gene interactions and pathways from curated databases and text-mining
Nature 1996, PMID: 8774881

Receptor-associated Mad homologues synergize as effectors of the TGF-beta response.

Zhang, Y; Feng, X; We, R; Derynck, R

Transforming growth factor-beta TGF-beta is the prototype for a family of extracellular proteins that affect cell proliferation and tissue differentiation. TGF-beta-related factors, including BMP-2/4, Dpp and activin, act through two types of serine/threonine kinase receptors which can form a heteromeric complex. However, the mechanism of signal transduction by these receptors is largely unknown. In Drosophila, Mad is required for signalling by Dpp. We have isolated complementary DNAs for four human Mad homologues, one of which, hMAD-4, is identical to DPC-4, a candidate tumour suppressor. hMAD-3 and -4 synergized to induce strong ligand-independent TGF-beta-like responses. When truncated at their carboxy termini, hMAD-3 and -4 act as dominant-negative inhibitors of the normal TGF-beta response. The activity of hMAD-3 and -4 was regulated by the TGF-beta receptors, and hMAD-3 but not hMAD-4 was phosphorylated and associated with the ligand-bound receptor complex. These results define hMAD-3 and -4 as effectors of the TGF-beta response and demonstrate a function for DPCA-4/hMAD-4 as a tumour suppressor.

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Text Mining Data

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Manually curated Databases

  • IRef Bind Interaction: SMAD3 — TGFBR1
  • IRef Bind Interaction: SMAD4 — TGFBR1
  • IRef Bind_translation Interaction: SMAD3 — TGFBR1 (experimental interaction detection)
  • IRef Bind_translation Interaction: TGFBR2 — SMAD4 (experimental interaction detection)
  • IRef Bind_translation Interaction: SMAD3 — TGFBR2 (experimental interaction detection)
  • IRef Bind_translation Interaction: TGFBR2 — TGFBR2 (experimental interaction detection)
  • IRef Bind_translation Interaction: SMAD4 — TGFBR1 (experimental interaction detection)
  • MIPS CORUM TGF-beta receptor-SMAD3 complex: TGF-beta receptor-SMAD3 complex complex (SMAD3-TGFBR1-TGFBR2)
  • IRef Corum Interaction: Complex of TGFBR1-TGFBR2-SMAD3 (association, coimmunoprecipitation)
  • Gene Ontology Complexes receptor complex: receptor complex complex (PTH1R-TAOK2-VLDLR-TGFBR2-GABRG1-KCTD8-EGFR-RET-NTRK1-RIPK1-INSR-TRPC1-INSRR-GABRA5-FLT4-ADCYAP1R1-GPR37-P2RX2-LOXL4-IMPG2-PKD1L3-NOTCH1-ADRA2A-TRADD-LRP2-MTTP-GPR101-ITLN1-VIPR1-CD200R1-GRM7-GPR84-FCRL5-RNMT-ITGB1-NPR1-SLITRK5-IL4R-KCTD12-PLA2R1-RAMP1-RXRA-RAMP2-PIGR-GPR62-GPR63-GPR61-ITPR3-GPR20-MTNR1A-ROR1-ABCG5-CR2-GPR37L1-LRP1-LRP6-KCTD16-LRP5-CR1L-NTRK2-APP-GABRQ-CSF1-ABCG8-ADRB2-ADRB3-TLR7-GPR119-TAS1R2)
  • IRef Hprd Interaction: TGFBR2 — SMAD4 (in vitro)
  • IRef Hprd Interaction: TGFBR2 — SMAD3 (in vitro)
  • IRef Hprd Interaction: TGFBR1 — SMAD4 (in vitro)
In total, 2352 gene pairs are associated to this article in curated databases