title: Post-translational regulation of TGF-β receptor and Smad signaling.
abstract: TGF-β family signaling through Smads is conceptually a simple and linear signaling pathway, driven by sequential phosphorylation, with type II receptors activating type I receptors, which in turn activate R-Smads. Nevertheless, TGF-β family proteins induce highly complex programs of gene expression responses that are extensively regulated, and depend on the physiological context of the cells. Regulation of TGF-β signaling occurs at multiple levels, including TGF-β activation, formation, activation and destruction of functional TGF-β receptor complexes, activation and degradation of Smads, and formation of Smad transcription complexes at regulatory gene sequences that cooperate with a diverse set of DNA binding transcription factors and coregulators. Here we discuss recent insights into the roles of post-translational modifications and molecular interaction networks in the functions of receptors and Smads in TGF-β signal responses. These layers of regulation demonstrate how a simple signaling system can be coopted to exert exquisitely regulated, complex responses.
authors.affiliation: Department of Cell and Tissue Biology, Programs in Cell Biology and Developmental Biology, University of California, San Francisco, CA, USA.
authors.forename: Pinglong
authors.initials: P
authors.lastname: Xu
authors.forename: Jianming
authors.initials: J
authors.lastname: Liu
authors.forename: Rik
authors.initials: R
authors.lastname: Derynck
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004705:Endocytosis; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025801:Ubiquitin; D004247:DNA