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Bone. 1999 Jul;25(1):91-3.

Signal transduction by bone morphogenetic protein receptors: functional roles of Smad proteins.

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Department of Biochemistry, The Cancer Institute, Japanese Foundation for Cancer Research, Japan Society for the Promotion of Science, Tokyo.


Intracellular signals for bone morphogenetic proteins (BMPs) and other members in the transforming growth factor (TGF)-beta superfamily are mediated by Smad proteins. Receptor-regulated Smads (R-Smads) are activated by serine/threonine kinase receptors upon ligand binding. R-Smads then form hetero-oligomeric complexes with a common-mediator Smad (co-Smad) and translocate into the nucleus, where they regulate transcription of target genes. Smads 1, 5, and 8 are R-Smads activated by BMP receptors, whereas Smads 2 and 3 are activated by TGF-beta and activin receptors. Smad4 is the only co-Smad isolated in mammals, and is shared by BMP and TGF-beta/activin signaling pathways. Smads 6 and 7 are anti-Smads, which block signals by preventing the activation of R-Smads by serine/threonine kinase receptors. Anti-Smads are induced by ligand stimulation, suggesting that they constitute a negative feedback loop in the signal transduction pathways of the TGF-beta superfamily.

[Indexed for MEDLINE]

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