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Gene interactions and pathways from curated databases and text-mining
J Cell Biol 2002, PMID: 12356868

TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2.

Hayes, Susan; Chawla, Anil; Corvera, Silvia

Transforming growth factor (TGF)beta is an important physiological regulator of cellular growth and differentiation. It activates a receptor threonine/serine kinase that phosphorylates the transcription factor Smad2, which then translocates into the nucleus to trigger specific transcriptional events. Here we show that activated type I and II TGF beta receptors internalize into endosomes containing the early endosomal protein EEA1. The extent of TGF beta-stimulated Smad2 phosphorylation, Smad2 nuclear translocation, and TGF beta-stimulated transcription correlated closely with the extent of internalization of the receptor. TGF beta signaling also requires SARA (Smad anchor for receptor activation), a 135-kD polypeptide that contains a FYVE Zn(++) finger motif. Here we show that SARA localizes to endosomes containing EEA1, and that disruption of this localization inhibits TGF beta-induced Smad2 nuclear translocation. These results indicate that traffic of the TGF beta receptor into the endosome enables TGF beta signaling, revealing a novel function for the endosome as a compartment specialized for the amplification of certain extracellular signals.

Document information provided by NCBI PubMed

Text Mining Data

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Manually curated Databases

  • 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
In total, 65 gene pairs are associated to this article in curated databases