title: Signal transduction by bone morphogenetic protein receptors: functional roles of Smad proteins.
abstract: 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.
authors.affiliation: Department of Biochemistry, The Cancer Institute, Japanese Foundation for Cancer Research, Japan Society for the Promotion of Science, Tokyo. miyazono-ind@umin.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Miyazono
mesh_terms: D000818:Animals; D052004:Bone Morphogenetic Protein Receptors; D004268:DNA-Binding Proteins / Q000502:physiology*; D005246:Feedback; D005810:Multigene Family; D011956:Receptors, Cell Surface / Q000502:physiology*; D017978:Receptors, Growth Factor; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D052004:Bone Morphogenetic Protein Receptors