Abstract |
The bone morphogenetic protein (BMP) signaling pathways have important roles in embryonic development and cellular homeostasis, with aberrant BMP signaling resulting in a broad spectrum of human disease. We report that BMPs unexpectedly signal through the canonical transforming growth factor β (TGF-β)-responsive Smad2 and Smad3. BMP-induced Smad2/3 signaling occurs preferentially in embryonic cells and transformed cells. BMPs signal to Smad2/3 by stimulating complex formation between the BMP-binding TGF-β superfamily receptors, activin receptor-like kinase (ALK)3/6, and the Smad2/3 phosphorylating receptors ALK5/7. BMP signaling through Smad2 mediates, in part, dorsoventral axis patterning in zebrafish embryos, whereas BMP signaling through Smad3 facilitates cancer cell invasion. Consistent with increased BMP-mediated Smad2/3 signaling during cancer progression, Smad1/5 and Smad 2/3 signaling converge in human cancer specimens. Thus, the signaling mechanisms used by BMPs and TGF-β superfamily receptors are broader than previously appreciated.
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Authors | Alisha Holtzhausen, Christelle Golzio, Tam How, Yong-Hun Lee, William P Schiemann, Nicholas Katsanis, Gerard C Blobe |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 28
Issue 3
Pg. 1248-67
(Mar 2014)
ISSN: 1530-6860 [Electronic] United States |
PMID | 24308972
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bone Morphogenetic Proteins
- Smad2 Protein
- Smad3 Protein
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Topics |
- Animals
- Bone Morphogenetic Proteins
(metabolism)
- Humans
- Phosphorylation
- Signal Transduction
- Smad2 Protein
(metabolism)
- Smad3 Protein
(metabolism)
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