Ski represses BMP signaling in Xenopus and mammalian cells
Journal Article
·
· Proceedings of the National Academy ofSciences
OSTI ID:908452
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.
- Research Organization:
- Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
- Sponsoring Organization:
- USDOE Director. Office of Science. Office of High Energy andNuclear Physics. Office of Basic Energy Sciences; American CancerSociety. March of Dimes, National Institutes of Health Grant GM49346,National Science Foundation
- DOE Contract Number:
- AC02-05CH11231
- OSTI ID:
- 908452
- Report Number(s):
- LBNL--47913; BnR: KC0302030
- Journal Information:
- Proceedings of the National Academy ofSciences, Journal Name: Proceedings of the National Academy ofSciences Journal Issue: 26 Vol. 97; ISSN 0027-8424; ISSN PNASA6
- Country of Publication:
- United States
- Language:
- English
Similar Records
Transcription regulation of the vegf gene by the BMP/Smad pathway in the angioblast of zebrafish embryos
Traf2 interacts with Smad4 and regulates BMP signaling pathway in MC3T3-E1 osteoblasts
Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation
Journal Article
·
Thu Mar 31 23:00:00 EST 2005
· Biochemical and Biophysical Research Communications
·
OSTI ID:20630912
Traf2 interacts with Smad4 and regulates BMP signaling pathway in MC3T3-E1 osteoblasts
Journal Article
·
Thu Dec 17 23:00:00 EST 2009
· Biochemical and Biophysical Research Communications
·
OSTI ID:22199920
Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation
Journal Article
·
Fri Jun 22 00:00:00 EDT 2012
· Biochemical and Biophysical Research Communications
·
OSTI ID:22207910