Gene interactions and pathways from curated databases and text-mining
J Cell Sci 2007, PMID: 17356069

Endofin acts as a Smad anchor for receptor activation in BMP signaling.

Shi, Weibin; Chang, Chenbei; Nie, Shuyi; Xie, Shutao; Wan, Mei; Cao, Xu

Signaling through receptors of the transforming growth factor beta (TGFbeta) superfamily is mediated by cytoplasmic Smad proteins. It has been demonstrated that Smad anchor for receptor activation (SARA) facilitates TGFbeta and activin/nodal signaling by recruiting and presenting Smad2/3 to the receptor complex. SARA does not bind Smad1 and hence does not enhance bone morphogenetic protein (BMP) signaling. Here we report for the first time that the endosome-associated FYVE-domain protein endofin acts as a Smad anchor for receptor activation in BMP signaling. We demonstrate that endofin binds Smad1 preferentially and enhances Smad1 phosphorylation and nuclear localization upon BMP stimulation. Silencing of endofin by RNAi resulted in a reduction in BMP-dependent Smad1 phosphorylation. Moreover, disruption of the membrane-anchoring FYVE motif by point mutation led to a reduction of BMP-responsive gene expression in cell culture and Xenopus ectodermal explants. Furthermore, we demonstrate that endofin contains a protein-phosphatase-binding motif, which functions to negatively modulate BMP signals through receptor dephosphorylation. Taken together, our results suggest that endofin plays an important role in both positive and negative feedback regulation of the BMP signaling pathway.

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Text Mining Data

BMP → Endofin: " Endofin acts as a Smad anchor for receptor activation in BMP signaling "

BMP → endofin: " Here we report for the first time that the endosome associated FYVE-domain protein endofin acts as a Smad anchor for receptor activation in BMP signaling "

Smad1 → endofin: " We demonstrate that endofin binds Smad1 preferentially and enhances Smad1 phosphorylation and nuclear localization upon BMP stimulation "

Smad1 ⊣ endofin: " Silencing of endofin by RNAi resulted in a reduction in BMP dependent Smad1 phosphorylation "

Smad1 → BMP: " Silencing of endofin by RNAi resulted in a reduction in BMP dependent Smad1 phosphorylation "

Manually curated Databases

  • MIPS Negatome - no physical interaction between proteins Interaction: SAR1A — SMAD1 (Absence of interaction, coimmunoprecipitation)
  • NCI Pathway Database BMP receptor signaling: BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2-ZFYVE16-PPP1CA-PPP1R15A) → ENDOFIN/SMAD1 complex (ZFYVE16-SMAD1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2-ZFYVE16-PPP1CA-PPP1R15A) → SMAD1 (SMAD1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2-ZFYVE16-PPP1CA-PPP1R15A) → GADD34/PP1CA complex (ZFYVE16-PPP1R15A-PPP1CA) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2-ZFYVE16-PPP1CA-PPP1R15A) → BMP2-4/BMPR2/BMPR1A-1B/RGM complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: ENDOFIN/SMAD1 complex (ZFYVE16-SMAD1) → SMAD1 (SMAD1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: ENDOFIN/SMAD1 complex (ZFYVE16-SMAD1) → GADD34/PP1CA complex (ZFYVE16-PPP1R15A-PPP1CA) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: ENDOFIN/SMAD1 complex (ZFYVE16-SMAD1) → BMP2-4/BMPR2/BMPR1A-1B/RGM complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: SMAD1 (SMAD1) → GADD34/PP1CA complex (ZFYVE16-PPP1R15A-PPP1CA) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: SMAD1 (SMAD1) → BMP2-4/BMPR2/BMPR1A-1B/RGM complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database BMP receptor signaling: GADD34/PP1CA complex (ZFYVE16-PPP1R15A-PPP1CA) → BMP2-4/BMPR2/BMPR1A-1B/RGM complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • Reactome Reaction: BMPR1B → SMAD5 (indirect_complex)
  • Reactome Reaction: SMAD1 → ZFYVE16 (reaction)
  • Reactome Reaction: BMP2 → SMAD9 (indirect_complex)
  • Reactome Reaction: BMPR2 → ZFYVE16 (reaction)
  • Reactome Reaction: ACVR2B → ZFYVE16 (indirect_complex)
  • Reactome Reaction: ACVR2B → BMP2 (indirect_complex)
  • Reactome Reaction: BMPR1A → SMAD5 (indirect_complex)
  • Reactome Reaction: SMAD5 → ZFYVE16 (reaction)
  • Reactome Reaction: ACVR2B → SMAD5 (reaction)
  • Reactome Reaction: SMAD9 → ZFYVE16 (direct_complex)
  • Reactome Reaction: ACVR2A → ZFYVE16 (reaction)
  • Reactome Reaction: ACVR2A → SMAD9 (reaction)
  • Reactome Reaction: BMPR2 → SMAD5 (reaction)
  • Reactome Reaction: BMPR2 → BMPR1B (indirect_complex)
  • Reactome Reaction: ACVR2A → SMAD5 (reaction)
  • Reactome Reaction: BMPR1B → SMAD9 (indirect_complex)
  • Reactome Reaction: ACVR2B → SMAD1 (reaction)
  • Reactome Reaction: ACVR2A → SMAD9 (indirect_complex)
  • Reactome Reaction: ACVR2B → BMPR1A (indirect_complex)
  • Reactome Reaction: BMPR1B → SMAD1 (reaction)
  • Reactome Reaction: BMPR1A → SMAD9 (indirect_complex)
  • Reactome Reaction: BMP2 → SMAD1 (reaction)
  • Reactome Reaction: BMPR2 → ZFYVE16 (indirect_complex)
  • Reactome Reaction: BMPR2 → SMAD9 (indirect_complex)
  • Reactome Reaction: BMPR1A → ZFYVE16 (indirect_complex)
  • Reactome Reaction: BMPR1A → SMAD1 (reaction)
  • Reactome Reaction: BMP2 → BMPR1A (indirect_complex)
  • Reactome Reaction: ACVR2A → BMP2 (indirect_complex)
  • Reactome Reaction: BMPR2 → SMAD1 (reaction)
  • Reactome Reaction: BMPR1B → SMAD5 (reaction)
  • Reactome Reaction: ACVR2B → SMAD9 (indirect_complex)
  • Reactome Reaction: SMAD9 → ZFYVE16 (reaction)
  • Reactome Reaction: BMPR2 → SMAD1 (indirect_complex)
  • Reactome Reaction: BMP2 → BMPR1B (indirect_complex)
  • Reactome Reaction: BMP2 → SMAD1 (indirect_complex)
  • Reactome Reaction: ACVR2A → BMPR1B (indirect_complex)
  • Reactome Reaction: ACVR2B → SMAD5 (indirect_complex)
  • Reactome Reaction: SMAD1 → ZFYVE16 (direct_complex)
  • Reactome Reaction: ACVR2A → ZFYVE16 (indirect_complex)
  • Reactome Reaction: BMP2 → BMPR2 (indirect_complex)
  • Reactome Reaction: BMPR2 → SMAD5 (indirect_complex)
  • Reactome Reaction: BMP2 → ZFYVE16 (indirect_complex)
  • Reactome Reaction: SMAD5 → ZFYVE16 (direct_complex)
  • Reactome Reaction: BMPR1B → ZFYVE16 (indirect_complex)
  • Reactome Reaction: ACVR2B → SMAD1 (indirect_complex)
  • Reactome Reaction: BMP2 → SMAD5 (reaction)
  • Reactome Reaction: ACVR2A → SMAD1 (reaction)
  • Reactome Reaction: BMPR1A → SMAD5 (reaction)
  • Reactome Reaction: ACVR2A → BMPR1A (indirect_complex)
  • Reactome Reaction: ACVR2B → SMAD9 (reaction)
  • Reactome Reaction: ACVR2A → SMAD5 (indirect_complex)
  • Reactome Reaction: BMPR1B → SMAD9 (reaction)
  • Reactome Reaction: BMP2 → SMAD9 (reaction)
  • Reactome Reaction: ACVR2A → SMAD1 (indirect_complex)
  • Reactome Reaction: BMP2 → SMAD5 (indirect_complex)
  • Reactome Reaction: BMPR1B → ZFYVE16 (reaction)
  • Reactome Reaction: ACVR2B → BMPR1B (indirect_complex)
  • Reactome Reaction: BMPR1A → SMAD1 (indirect_complex)
  • Reactome Reaction: BMPR1A → SMAD9 (reaction)
  • Reactome Reaction: BMP2 → ZFYVE16 (reaction)
  • Reactome Reaction: BMPR1B → SMAD1 (indirect_complex)
  • Reactome Reaction: ACVR2B → ZFYVE16 (reaction)
  • Reactome Reaction: BMPR2 → BMPR1A (indirect_complex)
  • Reactome Reaction: BMPR1A → ZFYVE16 (reaction)
  • Reactome Reaction: BMPR2 → SMAD9 (reaction)
In total, 103 gene pairs are associated to this article in curated databases