Abstract
Transforming growth factor beta (TGF-beta) initiates its diverse cellular responses by binding to and activating specific cell surface receptors that have intrinsic serine/threonine kinase activity. These activated TGF-beta receptors stimulate the phosphorylation of receptor-regulated Smad proteins, which in turn form complexes with Smad4 that accumulate in the nucleus and regulate the transcription of target genes. TGF-beta responses can be cell-type specific and are dependent on both the concentration of TGF-beta signalling components and the activity of other signal transduction pathways, which can either synergize with or antagonize the TGF-beta pathway. Recent research has provided insights into the specificity determinants of TGF-beta-Smad signalling, including combinatorial ligand-receptor associations, selective interactions between the Smads and other pathway components that are mediated through defined binding motifs, and the differential regulation of duration and intensity of signalling.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Active Transport, Cell Nucleus
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Activin Receptors / physiology
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Cell Nucleus / metabolism
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Cytoplasm / metabolism
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / physiology
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Humans
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Models, Biological
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Models, Molecular
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Phosphoproteins / physiology
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Protein Binding
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction / physiology*
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Smad Proteins
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Smad2 Protein
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Smad3 Protein
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Smad4 Protein
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Smad5 Protein
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Smad6 Protein
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Smad7 Protein
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Smad8 Protein
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Trans-Activators / chemistry
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Trans-Activators / physiology
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Transforming Growth Factor beta / physiology*
Substances
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DNA-Binding Proteins
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Phosphoproteins
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SMAD2 protein, human
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SMAD3 protein, human
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SMAD4 protein, human
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SMAD5 protein, human
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SMAD6 protein, human
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SMAD7 protein, human
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SMAD9 protein, human
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Smad Proteins
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Smad2 Protein
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Smad3 Protein
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Smad4 Protein
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Smad4 protein, rat
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Smad5 Protein
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Smad6 Protein
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Smad7 Protein
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Smad8 Protein
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Trans-Activators
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Transforming Growth Factor beta
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Protein Serine-Threonine Kinases
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Activin Receptors