Gene interactions and pathways from curated databases and text-mining
Genes Dev 1997, PMID: 9136927

The TGF-beta family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase.

Kretzschmar, M; Liu, F; Hata, A; Doody, J; Massagué, J

Bone morphogenetic proteins (BMPs) are members of the TGF-beta family that regulate cell proliferation, apoptosis, and differentiation, and participate in the development of most tissues and organs in vertebrates. Smad proteins function downstream of TGF-beta receptor serine/threonine kinases and undergo serine phosphorylation in response to receptor activation. Smad1 is regulated in this fashion by BMP receptors, and Smad2 and Smad3 by TGF-beta and activin receptors. Here, we report that BMP receptors phosphorylate and activate Smad1 directly. Phosphorylation of Smad1 in vivo involves serines in the carboxy-terminal motif SSXS. These residues are phosphorylated directly by a BMP type I receptor in vitro. Mutation of these carboxy-terminal serines prevents several Smad1 activation events, namely, Smad1 association with the related protein DPC4, accumulation in the nucleus, and gain of transcriptional activity. Similar carboxy-terminal serines in Smad2 are required for its phosphorylation and association with DPC4 in response to TGF-beta, indicating the generality of this process of Smad activation. As a direct physiological substrate of BMP receptors, Smad1 provides a link between receptor serine/threonine kinases and the nucleus.

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Text Mining Data

Smad1 → BMP: " Smad1 is regulated in this fashion by BMP receptors, and Smad2 and Smad3 by TGF-beta and activin receptors "

Smad1 → Smad2: " Smad1 is regulated in this fashion by BMP receptors, and Smad2 and Smad3 by TGF-beta and activin receptors "

Smad1 → Smad3: " Smad1 is regulated in this fashion by BMP receptors, and Smad2 and Smad3 by TGF-beta and activin receptors "

Smad1 → BMP: " Here, we report that BMP receptors phosphorylate and activate Smad1 directly "

Manually curated Databases

  • IRef Biogrid Interaction: BMPR1A — SMAD1 (direct interaction, enzymatic study)
  • IRef Hprd Interaction: TGFBR1 — SMAD1 (in vivo)
  • IRef Hprd Interaction: TGFBR1 — SMAD1 (in vitro)
  • IRef Hprd Interaction: ACVR1 — SMAD1 (in vivo)
  • IRef Hprd Interaction: ACVR1 — SMAD1 (in vitro)
  • 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
  • NCI Pathway Database BMP receptor signaling: SMAD7/SMURF1 complex (SMAD7-SMURF1) → SMAD1 (SMAD1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD7/SMURF1 complex (SMAD7-SMURF1) → BMP2-4/BMPR2/BMPR1A-1B/RGM complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD7/SMURF1 complex (SMAD7-SMURF1) → BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1 complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2-SMAD7-SMURF1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • 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
  • NCI Pathway Database BMP receptor signaling: SMAD1 (SMAD1) → BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1 complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2-SMAD7-SMURF1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: BMP2-4/BMPR2/BMPR1A-1B/RGM complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2) → BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1 complex (BMP4_BMP2-BMPR2-BMPR1A_BMPR1B-RGMB_RGMA_HFE2-SMAD7-SMURF1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1 complex (BMP7-BMPR2-BMPR1A_BMPR1B-SMAD6-SMURF1) → SMAD6/SMURF1 complex (SMAD6-SMURF1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1 complex (BMP7-BMPR2-BMPR1A_BMPR1B-SMAD6-SMURF1) → SMAD1 (SMAD1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1 complex (BMP7-BMPR2-BMPR1A_BMPR1B-SMAD6-SMURF1) → BMP7/BMPR2/BMPR1A-1B complex (BMP7-BMPR2-BMPR1A_BMPR1B) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD6/SMURF1 complex (SMAD6-SMURF1) → SMAD1 (SMAD1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD6/SMURF1 complex (SMAD6-SMURF1) → BMP7/BMPR2/BMPR1A-1B complex (BMP7-BMPR2-BMPR1A_BMPR1B) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD1 (SMAD1) → BMP7/BMPR2/BMPR1A-1B complex (BMP7-BMPR2-BMPR1A_BMPR1B) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD6-7/SMURF1/SMAD1 complex (SMAD6_SMAD7-SMURF1-SMAD1) → NUP214 (NUP214) (translocation, inhibits)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database BMP receptor signaling: SMAD1/SMAD1/SMAD4 complex (SMAD1-SMAD4) → SMAD4 (SMAD4) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD1/SMAD1/SMAD4 complex (SMAD1-SMAD4) → SMAD1 (SMAD1) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD1/SMAD1/SMAD4 complex (SMAD1-SMAD4) → SMAD6 (SMAD6) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD1/SMAD1/SMAD4 complex (SMAD1-SMAD4) → SMAD1/SMAD6 complex (SMAD1-SMAD6) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD4 (SMAD4) → SMAD1 (SMAD1) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD4 (SMAD4) → SMAD6 (SMAD6) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD4 (SMAD4) → SMAD1/SMAD6 complex (SMAD1-SMAD6) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD1 (SMAD1) → SMAD6 (SMAD6) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD1 (SMAD1) → SMAD1/SMAD6 complex (SMAD1-SMAD6) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD6 (SMAD6) → SMAD1/SMAD6 complex (SMAD1-SMAD6) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • Reactome Reaction: BMPR1B → SMAD5 (indirect_complex)
  • Reactome Reaction: ACVR2B → BMPR1A (reaction)
  • Reactome Reaction: SMAD1 → ZFYVE16 (reaction)
  • Reactome Reaction: BMP2 → SMAD9 (indirect_complex)
  • Reactome Reaction: BMPR2 → ZFYVE16 (reaction)
  • Reactome Reaction: BMPR1A → BMPR1B (reaction)
  • Reactome Reaction: ACVR2B → ZFYVE16 (indirect_complex)
  • Reactome Reaction: ACVR2B → BMP2 (indirect_complex)
  • Reactome Reaction: ACVR2A → BMPR1A (reaction)
  • 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: BMP2 → BMP2 (reaction)
  • 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: BMP2 → BMPR1A (reaction)
  • Reactome Reaction: BMPR2 → SMAD1 (reaction)
  • Reactome Reaction: BMPR2 → BMPR1B (reaction)
  • Reactome Reaction: BMPR1B → SMAD5 (reaction)
  • Reactome Reaction: ACVR2B → SMAD9 (indirect_complex)
  • Reactome Reaction: ACVR2A → BMPR2 (reaction)
  • Reactome Reaction: BMPR2 → BMPR1A (reaction)
  • 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: BMP2 → BMPR2 (reaction)
  • Reactome Reaction: BMPR2 → BMPR2 (reaction)
  • 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: ACVR2A → ACVR2B (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: ACVR2B → BMPR1B (reaction)
  • Reactome Reaction: BMP2 → SMAD9 (reaction)
  • Reactome Reaction: ACVR2A → BMPR1B (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 → BMPR1A (reaction)
  • Reactome Reaction: BMPR1A → SMAD1 (indirect_complex)
  • Reactome Reaction: BMPR1A → SMAD9 (reaction)
  • Reactome Reaction: ACVR2A → BMP2 (reaction)
  • Reactome Reaction: ACVR2B → BMPR2 (reaction)
  • Reactome Reaction: BMP2 → ZFYVE16 (reaction)
  • Reactome Reaction: ACVR2A → ACVR2A (reaction)
  • Reactome Reaction: BMPR1B → BMPR1B (reaction)
  • Reactome Reaction: ACVR2B → BMP2 (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: ACVR2B → ACVR2B (reaction)
  • Reactome Reaction: BMPR2 → SMAD9 (reaction)
  • Reactome Reaction: BMP2 → BMPR1B (reaction)
In total, 150 gene pairs are associated to this article in curated databases