Gene interactions and pathways from curated databases and text-mining
Proc Natl Acad Sci U S A 2000, PMID: 11121043

Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells.

Wang, W; Mariani, F V; Harland, R M; Luo, K

The bone morphogenic proteins (BMPs) play important roles in vertebrate development. In Xenopus, BMPs act as epidermal inducers and also as negative regulators of neurogenesis. Antagonism of BMP signaling results in neuralization. BMPs signal through the cell-surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. Here, we show that the Ski oncoprotein can block BMP signaling and the expression of BMP-responsive genes in both Xenopus and mammalian cells by directly interacting with and repressing the activity of BMP-specific Smad complexes. This ability to antagonize BMP signaling results in neuralization by Ski in the Xenopus embryo and blocking of osteoblast differentiation of murine W-20-17 cells. Thus, Ski is able to repress the activity of all receptor-associated Smads and may regulate vertebrate development by modulating the signaling activity of transforming growth factor-beta family members.

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Text Mining Data

Smad8 → BMP: " Upon stimulation with BMP , Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes "

Smad1 → BMP: " Upon stimulation with BMP , Smad1 , Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes "

Smad4 → BMP: " Upon stimulation with BMP , Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4 , and translocate into the nucleus, where they regulate the expression of BMP target genes "

Smad5 → BMP: " Upon stimulation with BMP , Smad1, Smad5 , and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes "

Manually curated Databases

  • NCI Pathway Database BMP receptor signaling: SKI (SKI) → SMAD5 (SMAD5) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database BMP receptor signaling: SKI (SKI) → SMAD5/SKI complex (SMAD5-SKI) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD5 (SMAD5) → SMAD5/SKI complex (SMAD5-SKI) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database BMP receptor signaling: SKI (SKI) → SMAD1 (SMAD1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database BMP receptor signaling: SKI (SKI) → SMAD1/SKI complex (SMAD1-SKI) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database BMP receptor signaling: SMAD1 (SMAD1) → SMAD1/SKI complex (SMAD1-SKI) (modification, collaborate)
    Evidence: physical interaction
  • Reactome Reaction: SKI → SMAD9 (direct_complex)
  • Reactome Reaction: SKI → SMAD9 (reaction)
  • Reactome Reaction: SKI → SMAD5 (reaction)
  • Reactome Reaction: SKI → SMAD1 (reaction)
  • Reactome Reaction: SKI → SMAD1 (direct_complex)
  • Reactome Reaction: SMAD4 → SMAD5 (direct_complex)
  • Reactome Reaction: SKI → SMAD4 (reaction)
  • Reactome Reaction: SKI → SMAD5 (direct_complex)
  • Reactome Reaction: SMAD4 → SMAD9 (direct_complex)
  • Reactome Reaction: SKI → SMAD4 (direct_complex)
  • Reactome Reaction: SMAD1 → SMAD4 (direct_complex)
In total, 10 gene pairs are associated to this article in curated databases