Smad3 allostery links TGF-β receptor kinase activation to transcriptional control
Open accessAbstract
Smad3 transduces the signals of TGF-βs, coupling transmembrane receptor kinase activation to transcriptional control. The membrane-associated molecule SARA (Smad Anchor for Receptor Activation) recruits Smad3 for phosphorylation by the receptor kinase. Upon phosphorylation, Smad3 dissociates from SARA and enters the nucleus, in which its transcriptional activity can be repressed by Ski. Here, we show that SARA and Ski recognize specifically the monomeric and trimeric forms of Smad3, respectively. Thus, trimerization of Smad3, induced by phosphorylation, simultaneously activates the TGF-β signal by driving Smad3 dissociation from SARA and sets up the negative feedback mechanism by Ski. Structural models of the Smad3/SARA/receptor kinase complex and Smad3/Ski complex provide insights into the molecular basis of regulation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
H-bond staples are not unique to MAPKAPK docking regions bound to MAPKs and are also used in other linear motif based interaction systems such as TGFβ signaling and DNA repair regulation.
“H-bond staples, however, are not unique to MAPKAPK docking regions bound to MAPKs and are also used in other linear motif based interaction systems such as those operating in TGFβ signaling (the TGFβ effector SMAD3 interacts with a linear motif in the adaptor SARA) or in DNA repair regulation (the DNA recombinase RAD51 interacts with a short peptide segment from the scaffold protein BRCA2 ) (39-41”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [39]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 51 · Cited by 139
- Authors
- Qin, B. Y., Lam, S. S., Correia, J. J., & Lin, K.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-08-01
- Volume
- 16
- Issue
- 15
- Pages
- 1950-1963
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC186427
- OpenAlex
- W2007977302
- Cited by
- 139
- References
- 51
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 6
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Brookhaven National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Smad3, TGF-beta signaling, SARA, skiing, allosteric regulation, Smad3 phosphorylation, Smad3 nuclear translocation, negative feedback regulation, transcriptional repression, structural model
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type I, Allosteric Regulation, Amino Acid Sequence, Binding Sites, Carrier Proteins, DNA-Binding Proteins, Enzyme Activation, Humans, Models, Molecular, Molecular Sequence Data, Phosphorylation, Protein Conformation, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Serine Endopeptidases, Transcription, Genetic, Trans-Activators, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Receptors, Transforming Growth Factor beta, Crystallography, X-Ray, Dimerization, Protein Interaction Mapping, Macromolecular Substances, Intracellular Signaling Peptides and Proteins, Smad3 Protein, Hydrophobic and Hydrophilic Interactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
