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The unique activity of bone morphogenetic proteins in bone: a critical role of the Smad signaling pathway by Takenobu Katagiri; Sho Tsukamoto is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract Bone morphogenetic proteins (BMPs) are multifunctional cytokines that belong to the transforming growth factor-β family. BMPs were originally identified based on their unique activity, inducing heterotopic bone formation in skeletal muscle. This unique BMP activity is transduced by specific type I and type II transmembrane kinase receptors. Among the downstream pathways activated by these receptors, the Smad1/5/8 transcription factors appear to play critical roles in BMP activity. Smad1/5/8 transcription factors are phosphorylated at the C-terminal SVS motif by BMP type I receptors and then induce the transcription of early BMP-responsive genes by binding to conserved sequences in their enhancer regions. The linker regions of Smad1/5/8 contain multiple kinase phosphorylation sites, and phosphorylation and dephosphorylation of these sites regulate the transcriptional activity of Smad proteins. Gain-of-function mutations in one BMP type I receptor have been identified in patients with fibrodysplasia ossificans progressiva, a rare genetic disorder that is characterized by progressive heterotopic bone formation in the skeletal muscle. The mutant receptors activate the Smad

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Author

Takenobu Katagiri; Sho Tsukamoto

Publisher

Walter de Gruyter GmbH

Published

2013

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)