Gene interactions and pathways from curated databases and text-mining
BMC cell biology 2006, PMID: 16571110

Smad7 and protein phosphatase 1alpha are critical determinants in the duration of TGF-beta/ALK1 signaling in endothelial cells.

Valdimarsdottir, Gudrun; Goumans, Marie-José; Itoh, Fumiko; Itoh, Susumu; Heldin, Carl-Henrik; ten Dijke, Peter

BACKGROUND

In endothelial cells (EC), transforming growth factor-beta (TGF-beta) can bind to and transduce signals through ALK1 and ALK5. The TGF-beta/ALK5 and TGF-beta/ALK1 pathways have opposite effects on EC behaviour. Besides differential receptor binding, the duration of TGF-beta signaling is an important specificity determinant for signaling responses. TGF-beta/ALK1-induced Smad1/5 phosphorylation in ECs occurs transiently.

RESULTS

The temporal activation of TGF-beta-induced Smad1/5 phosphorylation in ECs was found to be affected by de novo protein synthesis, and ALK1 and Smad5 expression levels determined signal strength of TGF-beta/ALK1 signaling pathway. Smad7 and protein phosphatase 1alpha (PP1alpha) mRNA expression levels were found to be specifically upregulated by TGF-beta/ALK1. Ectopic expression of Smad7 or PP1alpha potently inhibited TGF-beta/ALK1-induced Smad1/5 phosphorylation in ECs. Conversely, siRNA-mediated knockdown of Smad7 or PP1alpha enhanced TGF-beta/ALK1-induced signaling responses. PP1alpha interacted with ALK1 and this association was further potentiated by Smad7. Dephosphorylation of the ALK1, immunoprecipitated from cell lysates, was attenuated by a specific PP1 inhibitor.

CONCLUSIONS

Our results suggest that upon its induction by the TGF-beta/ALK1 pathway, Smad7 may recruit PP1alpha to ALK1, and thereby control TGF-beta/ALK1-induced Smad1/5 phosphorylation.

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Text Mining Data

Smad1/5 → TGF-beta/ALK1: " TGF-beta/ALK1 induced Smad1/5 phosphorylation in ECs occurs transiently "

Smad1/5 → TGF-beta/ALK1: " TGF-beta/ALK1 induced Smad1/5 phosphorylation in ECs occurs transiently "

Smad1/5 ⊣ Smad7: " Ectopic expression of Smad7 or PP1alpha potently inhibited TGF-beta/ALK1 induced Smad1/5 phosphorylation in ECs "

Smad1/5 ⊣ PP1alpha: " Ectopic expression of Smad7 or PP1alpha potently inhibited TGF-beta/ALK1 induced Smad1/5 phosphorylation in ECs "

Smad1/5 ⊣ Smad7: " Ectopic expression of Smad7 or PP1alpha potently inhibited TGF-beta/ALK1 induced Smad1/5 phosphorylation in ECs "

Smad1/5 ⊣ PP1alpha: " Ectopic expression of Smad7 or PP1alpha potently inhibited TGF-beta/ALK1 induced Smad1/5 phosphorylation in ECs "

Smad1/5 → TGF-beta/ALK1: " Ectopic expression of Smad7 or PP1alpha potently inhibited TGF-beta/ALK1 induced Smad1/5 phosphorylation in ECs "

Smad1/5 → TGF-beta/ALK1: " Ectopic expression of Smad7 or PP1alpha potently inhibited TGF-beta/ALK1 induced Smad1/5 phosphorylation in ECs "

Smad1/5 → TGF-beta/ALK1: " Our results suggest that upon its induction by the TGF-beta/ALK1 pathway, Smad7 may recruit PP1alpha to ALK1, and thereby control TGF-beta/ALK1 induced Smad1/5 phosphorylation "

Smad1/5 → TGF-beta/ALK1: " Our results suggest that upon its induction by the TGF-beta/ALK1 pathway, Smad7 may recruit PP1alpha to ALK1, and thereby control TGF-beta/ALK1 induced Smad1/5 phosphorylation "

Manually curated Databases

  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CAV1 complex (TGFBR2-TGFBR1-ACVRL1-CAV1-ENG-TGFB1) → SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CAV1 complex (TGFBR2-TGFBR1-ACVRL1-CAV1-ENG-TGFB1) → TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/PPP1CA complex (TGFBR2-TGFBR1-ACVRL1-PPP1CA-ENG-TGFB1) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CAV1 complex (TGFBR2-TGFBR1-ACVRL1-CAV1-ENG-TGFB1) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/PPP1CA complex (TGFBR2-TGFBR1-ACVRL1-PPP1CA-ENG-TGFB1) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, inhibits)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: PPP1CA (PPP1CA) → SMAD7 (SMAD7) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database ALK1 signaling events: PPP1CA (PPP1CA) → TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/PPP1CA complex (TGFBR2-TGFBR1-ACVRL1-PPP1CA-ENG-TGFB1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database ALK1 signaling events: PPP1CA (PPP1CA) → TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1 complex (TGFBR2-TGFBR1-ACVRL1-ENG-TGFB1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database ALK1 signaling events: SMAD7 (SMAD7) → TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/PPP1CA complex (TGFBR2-TGFBR1-ACVRL1-PPP1CA-ENG-TGFB1) (modification, activates)
    Evidence: physical interaction
  • NCI Pathway Database ALK1 signaling events: SMAD7 (SMAD7) → TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1 complex (TGFBR2-TGFBR1-ACVRL1-ENG-TGFB1) (modification, activates)
    Evidence: physical interaction
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/PPP1CA complex (TGFBR2-TGFBR1-ACVRL1-PPP1CA-ENG-TGFB1) → TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1 complex (TGFBR2-TGFBR1-ACVRL1-ENG-TGFB1) (modification, collaborate)
    Evidence: physical interaction
In total, 60 gene pairs are associated to this article in curated databases