Affinage

SMAD2

SMAD family member 2 · UniProt Q15796

Length
467 aa
Mass
52.3 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMAD2 is a receptor-regulated transcription factor that transduces TGF-β/activin/Nodal signals from the cell surface to the nucleus to control mesoderm induction, embryonic axis formation, and tissue homeostasis (PMID:8980228, PMID:8756346, PMID:10535967). Upon activation of the TGF-β type I receptor by the type II receptor kinase, SMAD2 is directly phosphorylated on C-terminal serines; mutation of these sites yields a dominant-negative protein that stays receptor-bound and fails to accumulate in the nucleus (PMID:8980228, PMID:9311995). In unstimulated cells SMAD2 is held cytoplasmic by the FYVE-domain scaffold SARA, which directly binds and recruits it to the receptor, while phosphorylation drives SARA dissociation, heterotrimer formation with SMAD4 (and SMAD3), and nuclear translocation (PMID:9865696, PMID:26905010). In the nucleus, DNA binding depends on the conformation of the SMAD2-specific E3 insert and is enhanced by p300/CBP/P/CAF-mediated acetylation of Lys19 in the MH1 domain, while the MH2 hydrophobic surfaces serve as combinatorial docking sites for cofactors such as FOXH1 and the corepressor SKI (PMID:17074756, PMID:29588413, PMID:31582430). SMAD2 activity is attenuated by linker-region phosphorylation (Araf, MAPKs, CDK2), by the phosphatase PPM1A, and by deacetylation and ubiquitin-mediated degradation through SIRT2/SMURF2 and interactors including CCT6A (PMID:23591895, PMID:34504019, PMID:36752205, PMID:37777567, PMID:28375158). SMAD2 and SMAD3 carry distinct and often opposing roles: SMAD2 is counter-regulatory in fibrosis (restraining SMAD3-driven collagen induction), both are required for myostatin/TGF-β- and Thbs1-driven muscle atrophy via ATF4/ALP/UPS, and SMAD2 can promote terminal myogenic differentiation independently of receptor activation (PMID:20595680, PMID:28891814, PMID:38678560, PMID:33462116). Cancer-derived inactivating mutations in SMAD2 abrogate TGF-β signaling, consistent with a tumor-suppressive role (PMID:8752209).

Mechanistic history

Synthesis pass · year-by-year structured walk · 35 steps
  1. 1996 High

    Established SMAD2 as the direct intracellular substrate of the activated TGF-β receptor, defining the entry point of the signaling cascade.

    Evidence In vitro phosphorylation, dominant-negative mutagenesis of C-terminal serines, and nuclear accumulation assays

    PMID:8980228

    Open questions at the time
    • Did not resolve heterotrimer composition or DNA-binding mechanism
    • Phosphatase/turnover regulation unaddressed
  2. 1996 High

    Defined pathway specificity (TGF-β vs BMP) and linked SMAD2 loss-of-function to human cancer through inactivating colorectal carcinoma mutations.

    Evidence Biochemical signaling specificity assays and functional analysis of cancer-derived point mutations

    PMID:8752209

    Open questions at the time
    • Mechanism by which mutations inactivate signaling not structurally defined at the time
  3. 1996 High

    Showed SMAD2 is a signal-dependent mesoderm inducer whose nuclear accumulation rises with activin, with separable activating and cytoplasmic-anchoring domains.

    Evidence Xenopus ectoderm functional assay and lacZ-Madr2 nuclear localization with domain deletions

    PMID:8756346

    Open questions at the time
    • Identity of the cytoplasmic anchor not yet known
    • Downstream transcriptional partners unidentified
  4. 1997 High

    Demonstrated heteromeric SMAD2/SMAD3/SMAD4 complex formation and cooperative nuclear transcriptional output, defining the effector complex.

    Evidence Reciprocal co-IP, immunofluorescence, and PAI-1 reporter assays with dominant-negative Smad3

    PMID:9311995

    Open questions at the time
    • Stoichiometry of the complex not resolved
    • Promoter recruitment cofactors not identified
  5. 1998 High

    Identified SARA as the cytoplasmic anchor that recruits SMAD2 to the receptor, explaining how localization gates signaling.

    Evidence Yeast two-hybrid/pulldown, co-IP, mislocalization mutants, and reporter assays

    PMID:9865696

    Open questions at the time
    • How phosphorylation releases SARA structurally unresolved
    • SARA regulation upstream not defined
  6. 1998 Medium

    Placed SMAD2 as a shared effector of RTK (HGF/EGF) signaling acting through MEK1-downstream kinases, broadening its input beyond TGF-β.

    Evidence Phosphorylation/nuclear translocation assays and dominant-negative epistasis

    PMID:9620846

    Open questions at the time
    • Direct kinase downstream of MEK1 not identified
    • Physiological relevance vs canonical TGF-β input unclear
  7. 1999 High

    Established an in vivo developmental requirement for SMAD2 in extraembryonic tissue for A-P axis formation, linking it to Hex expression.

    Evidence Smad2 null mouse knockout, chimeric rescue, and Hex in situ hybridization

    PMID:10535967

    Open questions at the time
    • Direct transcriptional targets driving axis formation not defined
    • Cell-autonomous vs non-autonomous contributions only partly resolved
  8. 2000 Medium

    Revealed calmodulin as a direct negative regulator coupling Ca2+ and Erk crosstalk to SMAD2 linker phosphorylation.

    Evidence Direct binding assays, Xenopus functional assays, and Erk2-dependent phosphorylation analysis

    PMID:11007779

    Open questions at the time
    • Mammalian physiological relevance not established
    • Quantitative contribution to signaling output unclear
  9. 2004 High

    Demonstrated cooperative SMAD2/SMAD3 dose-dependent function in craniofacial and endodermal development through genetic interaction.

    Evidence Compound heterozygous Smad2/Smad3 knockout mice with histology and expression analysis

    PMID:15183723

    Open questions at the time
    • Distinct vs redundant target genes not parsed
    • Molecular basis of endoderm displacement failure unresolved
  10. 2006 High

    Identified acetylation of Lys19 by p300/CBP/P/CAF as a TGF-β-dependent activating modification that enhances DNA binding via conformational change.

    Evidence In vitro acetylation, acetyl-Lys19 antibody, ChIP, and Lys19 mutagenesis with DNA-binding assays

    PMID:17074756

    Open questions at the time
    • Reversal/deacetylase not identified at the time
    • Interplay with phosphorylation kinetics not mapped
  11. 2007 Medium

    Showed SMAD2 protein stability is set by ubiquitin/proteasome turnover, with endoglin potentiating signaling by reducing degradation.

    Evidence Endoglin siRNA, ubiquitination assays, protein vs mRNA Westerns, and reporter assays

    PMID:17058229

    Open questions at the time
    • E3 ligase mediating degradation not identified here
    • Direct vs indirect endoglin effect unresolved
  12. 2009 Medium

    Placed SMAD2/3 as transcriptional drivers of myostatin/TGF-β-induced muscle atrophy, with inhibition driving mTOR-dependent hypertrophy.

    Evidence Dominant-negative constructs in adult myofibers with muscle mass and mTOR analysis

    PMID:19357234

    Open questions at the time
    • Direct atrophy target genes not defined here
    • SMAD2 vs SMAD3 contribution not separated
  13. 2010 High

    Reframed SMAD2 as a counter-regulatory brake on SMAD3-driven fibrosis, restraining Smad3 phosphorylation and COL1A2 promoter binding.

    Evidence Conditional tubular Smad2 KO (UUO model), overexpression rescue, and Smad3 ChIP on COL1A2

    PMID:20595680

    Open questions at the time
    • Molecular mechanism of SMAD2 restraint on SMAD3 phosphorylation not fully defined
    • Generalizability across fibrotic tissues addressed only later
  14. 2013 High

    Identified Araf as a linker-region kinase (Ser253) that accelerates degradation of activated SMAD2, antagonizing Nodal/SMAD2 mesendoderm induction.

    Evidence In vitro kinase assay, S253 mutagenesis, co-IP, and zebrafish araf knockdown

    PMID:23591895

    Open questions at the time
    • Mammalian Araf-SMAD2 axis relevance not established
    • Degradation machinery downstream of linker phosphorylation not fully defined
  15. 2013 Medium

    Showed PAK4 dually regulates SMAD2 — kinase-independent blockade of C-terminal phosphorylation and kinase-dependent degradation under HGF.

    Evidence Co-IP, kinase assays, DN/CA PAK4 constructs, ubiquitin-proteasome degradation assays, and gastric cancer IHC

    PMID:23934187

    Open questions at the time
    • Single lab; reciprocal in vivo validation limited
    • Switch between the two mechanisms not quantitatively defined
  16. 2015 Medium

    Defined opposing SMAD2 vs SMAD3 roles in dendritic cell TGF-β autoinduction, with SMAD2 loss producing tolerogenic, TGF-β-high DCs.

    Evidence Conditional Smad2-deficient DCs, TGF-β expression assay, and colitis model

    PMID:26141582

    Open questions at the time
    • Direct promoter mechanism of SMAD2 repression of TGF-β not mapped
    • Single-lab in vivo immune model
  17. 2015 Medium

    Established SMAD2 (not SMAD3) as a transcriptional repressor at the BECN1 promoter controlling endothelial autophagy.

    Evidence SMAD2 siRNA, BECN1 reporter assays, endoglin perturbation, and autophagy quantification

    PMID:25931117

    Open questions at the time
    • Corepressor identity at BECN1 not defined
    • Direct binding to BECN1 promoter element not mapped
  18. 2016 High

    Defined non-redundant SMAD2 vs SMAD3 promoter logic in chondrogenesis, with SMAD2 recruiting Hdac4 and SMAD3 recruiting Ski at distinct Ihh SBEs.

    Evidence Cartilage-specific Smad2 KO and global Smad3 KO, ChIP for Smad2/3 and Hdac4, and SBE mutagenesis

    PMID:27741240

    Open questions at the time
    • Determinants of differential SBE selectivity not structurally defined
    • Generalization to other promoters unclear
  19. 2016 Medium

    Explained the functional divergence of SMAD2 and SMAD3 by their distinct basal localization and oligomerization, with SMAD3's linker impairing SMAD4 binding.

    Evidence Subcellular fractionation, immunofluorescence, SMAD4 co-IP, and ChIP-seq

    PMID:26905010

    Open questions at the time
    • Structural basis of localization difference not resolved here
    • Single-lab observations
  20. 2017 Medium

    Identified CCT6A as a direct SMAD2 binder that switches TGF-β output from tumor-suppressive SMAD2 to prometastatic SMAD3 programs.

    Evidence Co-IP, SMAD2/CCT6A knockdown, transcriptional and invasion/metastasis assays in NSCLC

    PMID:28375158

    Open questions at the time
    • Mechanism of SMAD2 suppression by CCT6A not biochemically resolved
    • Single-lab models
  21. 2017 High

    Genetically dissected SMAD2 vs SMAD3 in cardiac fibrosis, showing SMAD3 (not SMAD2) drives fibroblast-mediated fibrosis.

    Evidence Fibroblast-specific inducible Smad2 or Smad3 KO in pressure-overload model

    PMID:28891814

    Open questions at the time
    • Molecular target genes distinguishing the two not detailed
    • SMAD2's positive role in this context limited
  22. 2018 High

    Provided structural basis for combinatorial cofactor binding, mapping MH2 hydrophobic patches used cooperatively/competitively by FOXH1 and SKI.

    Evidence X-ray crystallography of SMAD3-FOXH1 and SMAD2-SKI complexes

    PMID:29588413

    Open questions at the time
    • Full repertoire of patch-binding cofactors not catalogued
    • Dynamics of cooperative/competitive switching not captured
  23. 2018 Medium

    Resolved linker-region phospho-site selectivity, linking specific residues and kinases to distinct GAG-synthesis gene programs downstream of thrombin.

    Evidence Site-directed mutagenesis of individual linker residues and selective kinase inhibitors with gene expression readout

    PMID:30423352

    Open questions at the time
    • Direct vs indirect transcriptional links not all established
    • Single-lab system
  24. 2019 High

    Overturned the view that SMAD2 cannot bind DNA, showing E3-insert conformation enables direct DNA binding while SMAD2 (unlike SMAD3) requires signaling for promoter recruitment.

    Evidence Crystal structure of SMAD2-DNA, biochemical DNA binding, ChIP-seq, and mouse mesendoderm genetics

    PMID:31582430

    Open questions at the time
    • Genome-wide determinants of SMAD2 vs SMAD3 site selection not fully mapped
    • Conformational trigger for E3 insert not defined
  25. 2019 Medium

    Identified WWP2 N-terminal isoform as a regulator of SMAD2 nucleocytoplasmic shuttling and transcriptional activity relevant to cardiac fibrosis.

    Evidence Co-IP, nuclear translocation assays, WWP2 N-terminal deletion transgenic mice, and cardiac fibroblast assays

    PMID:31399586

    Open questions at the time
    • Whether WWP2 ubiquitinates SMAD2 directly not resolved
    • Single-lab mechanism
  26. 2020 High

    Defined SIRT2 as a SMAD2 deacetylase (K451) that promotes SMURF2-dependent ubiquitination and degradation, coupling deacetylation to turnover.

    Evidence Co-IP, in vitro deacetylation with site mapping, ubiquitination assays, SMURF2 epistasis, and renal Sirt2 KO

    PMID:37777567

    Open questions at the time
    • Interplay of K451 with activating Lys19 acetylation not integrated
    • Tissue scope beyond kidney unclear
  27. 2020 Medium

    Showed LSD1 co-recruits with phospho-SMAD2/3 to EMT gene promoters, priming activation/repression through a nuclear oxidative wave.

    Evidence ChIP for co-recruitment, confocal/mass spectrometry for DNA oxidation, and co-IP

    PMID:32697292

    Open questions at the time
    • Causal link between DNA oxidation and transcription not fully established
    • Single-lab
  28. 2020 Medium

    Identified MED1 as a SMAD2 interactor whose loss stabilizes SMAD2 to promote SMAD2-dependent EMT and melanoma metastasis.

    Evidence Co-IP, ubiquitination assays, MED1 perturbation with EMT/migration readouts, and metastasis model

    PMID:35131256

    Open questions at the time
    • Mechanism by which MED1 promotes SMAD2 degradation unresolved
    • Single-lab
  29. 2020 Medium

    Showed mutant FOXL2C134W gains capacity to assemble a FOXL2/SMAD4/SMAD2-3 complex on a novel hybrid motif driving EMT gene expression.

    Evidence Co-IP, ChIP-seq for hybrid motif, and SMAD4/SMAD2-3 knockdown epistasis

    PMID:32641411

    Open questions at the time
    • SMAD2-specific vs SMAD3-specific contribution not separated
    • Single-lab
  30. 2021 Medium

    Showed SMAD2 can drive terminal myogenic differentiation and myogenin expression independently of TGF-β receptor activation.

    Evidence SMAD2 KO/overexpression in primary myoblasts and satellite-cell-specific Smad2 KO with regeneration assays

    PMID:33462116

    Open questions at the time
    • How receptor-independent SMAD2 is activated not defined
    • Direct myogenin promoter interaction not mapped
  31. 2021 Medium

    Linked creatine/MPS1-mediated SMAD2/3 phosphorylation to Snail/Slug induction and metastasis.

    Evidence MPS1 inhibition, GATM knockdown, phospho-SMAD2/3 Westerns, and orthotopic metastasis models

    PMID:33811821

    Open questions at the time
    • Direct MPS1 phosphorylation site on SMAD2 not mapped
    • Single-lab
  32. 2021 Medium

    Showed fluid-shear-stress control of SMAD2/3 acts at nuclear translocation via MEKK3/Klf2 and CDK2-dependent linker phosphorylation, decoupling phosphorylation from nuclear entry.

    Evidence EC-specific ALK5 deletion, nuclear translocation imaging, and CDK2/Klf2 inhibition in flow models

    PMID:34504019

    Open questions at the time
    • Mechanistic link between linker phosphorylation and translocation block not detailed
    • Single-lab
  33. 2022 Medium

    Linked mitochondrial dysfunction to MAPK-mediated SMAD2 phosphorylation enhancing ALK5-SMAD2 signaling in endothelial vascular pathology.

    Evidence Endothelial Smad2 KO rescuing three mitochondrial KO models, ALK5 inhibition, and fractionation

    PMID:36496409

    Open questions at the time
    • Mitochondrial SMAD2 localization mechanism only partly supported
    • Single-lab
  34. 2023 High

    Established PPM1A as a direct SMAD2 phosphatase whose loss sustains p-SMAD2 and protects cartilage, with rescue by TGF-β/SMAD2 inhibition.

    Evidence Co-IP, PPM1A conditional KO in DMM model, and pharmacological rescue with SD-208

    PMID:36752205

    Open questions at the time
    • Selectivity of PPM1A for SMAD2 vs SMAD3 not detailed
    • Structural basis of recognition unresolved
  35. 2024 High

    Defined a Thbs1→TGF-β-SMAD2/3→ATF4→ALP/UPS axis driving muscle atrophy, with myofiber Smad2/3 deletion conferring protection.

    Evidence Myofiber-specific Smad2/Smad3 double KO, Thbs1 and ATF4 mouse models, and ALP/UPS activity assays

    PMID:38678560

    Open questions at the time
    • SMAD2 vs SMAD3 individual contribution within the axis not separated
    • Direct ATF4 promoter regulation by SMAD2 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the combinatorial code of SMAD2 post-translational modifications (Lys19/K451 acetylation, multi-site linker phosphorylation), E3-insert conformation, and cofactor patch occupancy is integrated to produce context-specific, SMAD2- vs SMAD3-divergent transcriptional outputs remains unresolved.
  • No unified model linking modification state to genome-wide site selection
  • Determinants of SMAD2 vs SMAD3 promoter partitioning incompletely defined
  • In vivo turnover regulators integrating SIRT2/SMURF2/WWP2/MED1 not reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060089 molecular transducer activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 5 GO:0005654 nucleoplasm 3 GO:0005829 cytosol 3
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4
Partners
CCT6AFOXH1PPM1ASARASIRT2SKISMAD3SMAD4
Complex memberships
FOXL2C134W/SMAD4/SMAD2-3 complexSMAD2-SKI corepressor complexSMAD2/SMAD3/SMAD4 heterotrimer

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 MADR2/SMAD2 is directly phosphorylated by the TGF-β receptor complex on C-terminal serines. Interaction requires activation of receptor I (TβRI) by receptor II (TβRII), mediated by the receptor I kinase. Mutation of the phosphorylation sites generates a dominant-negative MADR2 that stably associates with receptors and fails to accumulate in the nucleus in response to TGF-β. In vitro phosphorylation assay, dominant-negative mutagenesis, nuclear accumulation assay, co-immunoprecipitation with receptors Cell High 8980228
1996 MADR2/SMAD2 is specifically regulated by TGF-β and not bone morphogenetic proteins. Missense mutations found in colorectal carcinomas are inactivating for TGF-β signaling. Biochemical signaling assays, functional analysis of cancer-derived point mutations Cell High 8752209
1996 Madr2/SMAD2 is a mesoderm inducer that responds to activin signaling; activin stimulation enhances nuclear concentration of Madr2 in Xenopus ectoderm. The C-terminal domain can activate downstream components independently, while an N-terminal repressive domain anchors the protein in the cytoplasm in the absence of signal. Xenopus ectoderm functional assay, lacZ/Madr2 fusion protein nuclear localization analysis, domain deletion experiments Genes & development High 8756346
1997 Smad2 and Smad3 interact with the kinase-deficient TGF-β type I receptor after it is phosphorylated by TβRII kinase. TGF-β1 induces phosphorylation of Smad2 and Smad3, and Smads 2 and 3 form heteromeric complexes with Smad4 after TβR activation. Smad2, Smad3 and Smad4 accumulate in the nucleus upon TGF-β1 treatment and show synergistic effects in transcriptional reporter assays. Co-immunoprecipitation in transfected COS cells, immunofluorescence nuclear localization, transcriptional reporter assay (PAI-1 promoter), dominant-negative Smad3 The EMBO journal High 9311995
1998 SARA (Smad anchor for receptor activation), a FYVE domain protein, directly interacts with Smad2 and Smad3 and recruits Smad2 to the TGF-β receptor by controlling subcellular localization. Phosphorylation of Smad2 induces dissociation from SARA with concomitant Smad2/Smad4 complex formation and nuclear translocation. SARA mutations causing mislocalization of Smad2 inhibit TGF-β-dependent transcriptional responses. Yeast two-hybrid/pulldown, co-immunoprecipitation, subcellular localization assay, dominant-negative SARA mutant functional assay, transcriptional reporter assay Cell High 9865696
1998 HGF and EGF, signaling through receptor tyrosine kinases, can also induce phosphorylation and nuclear translocation of Smad2 via kinase(s) downstream of MEK1. A mutation in Smad2 that blocks TGF-β signaling also blocks HGF signal transduction, placing Smad2 as a common effector of both RTK and TGF-β receptor pathways. Epitope-tagged Smad2 phosphorylation and nuclear translocation assay, SMAD-dependent reporter gene activation, dominant-negative Smad2 epistasis Genes & development Medium 9620846
1999 SMAD2 is required in extraembryonic tissues for generation of the anterior-posterior axis and gastrulation. Postgastrulation Smad2-deficient embryos show malformation of head structures, abnormal embryo turning, and cyclopia, and expression of the homeobox gene Hex (earliest A-P polarity marker) is absent in Smad2-deficient embryos. Smad2 null mouse knockout, chimeric embryo rescue by wild-type extraembryonic tissues, in situ hybridization for Hex expression Proceedings of the National Academy of Sciences of the United States of America High 10535967
2000 Calmodulin directly binds to two distinct conserved regions in Smad2 and inhibits Smad2 function in Xenopus embryos. Calmodulin binding to Smad2 inhibits subsequent Erk2-dependent linker region phosphorylation of Smad2, and vice versa, indicating cross-talk between Ca2+/calmodulin, RTK/Erk, and TGF-β pathways at the level of Smad2. Direct binding assay (calmodulin-Smad interaction), Xenopus embryo functional assay, structure-function analysis with domain deletions, Erk2-dependent phosphorylation assay The Journal of biological chemistry Medium 11007779
2004 Smad2 and Smad3 function cooperatively in craniofacial and endodermal development. Compound heterozygous mice (one allele each of Smad2 and Smad3 null) show craniofacial defects and hepatic phenotypes due to defects in the definitive endoderm, including failure to displace visceral endoderm. Genetic epistasis via compound heterozygous mouse knockout, histology, gene expression analysis Developmental biology High 15183723
2006 Smad2 acetylation by coactivators p300, CBP, and P/CAF occurs in a TGF-β-dependent manner. The major acetylated residue in both the long and short isoforms of Smad2 is Lys19 in the MH1 domain. Acetylation of Lys19 in the short isoform improves DNA binding activity in vitro, enhances association with target promoters in vivo, and augments transcriptional activity by inducing a conformational change making the DNA-binding domain accessible. In vitro acetylation assay, acetyl-Lys19-specific antibody detection of endogenous acetylation, chromatin immunoprecipitation (ChIP), site-directed mutagenesis of Lys19, DNA binding assay The Journal of biological chemistry High 17074756
2007 Endoglin increases Smad2 protein levels by decreasing ubiquitination and proteasome-dependent degradation, thereby stabilizing Smad2 and potentiating TGF-β-Smad2 signaling to increase eNOS expression in endothelial cells. Smad2-specific signaling is upregulated by endoglin and downregulated when endoglin is knocked down with siRNA. siRNA knockdown of endoglin, dominant-negative Smad2, ubiquitination assay, Western blot for Smad2 protein levels vs. mRNA, eNOS and PAI-promoter reporter assay Journal of cellular physiology Medium 17058229
2009 Smad2 and Smad3 are transcription factors downstream of myostatin/TGF-β that induce a muscle atrophy program in adult myofibers. Smad2/3 inhibition promotes muscle hypertrophy in a manner independent of satellite cells but partially dependent on mTOR signaling. In vivo genetic perturbation with dominant-negative constructs in adult myofibers, muscle mass measurement, mTOR signaling analysis American journal of physiology. Cell physiology Medium 19357234
2010 Smad2 protects against TGF-β/Smad3-mediated renal fibrosis. Conditional deletion of Smad2 from kidney tubular epithelial cells markedly enhanced fibrosis, and Smad2 deletion promoted fibrosis through enhanced TGF-β/Smad3 signaling evidenced by greater Smad3 phosphorylation, nuclear translocation, and binding of Smad3 to the COL1A2 promoter. Conversely, overexpression of Smad2 attenuated TGF-β1-induced Smad3 phosphorylation. Conditional Smad2 knockout in tubular epithelial cells (unilateral ureteral obstruction model), Smad2 overexpression, Smad3 ChIP on COL1A2 promoter, Western blot for phospho-Smad3 Journal of the American Society of Nephrology : JASN High 20595680
2013 Araf kinase directly binds to and phosphorylates Smad2 in the linker region with Ser253 being indispensable, in a Mek/Erk-independent manner. This linker phosphorylation attenuates Smad2 signaling by accelerating degradation of activated Smad2 and antagonizes mesendoderm induction by Nodal/Smad2 in zebrafish embryos. Direct in vitro kinase assay (Araf phosphorylates Smad2), site-directed mutagenesis of S253, co-immunoprecipitation (Araf-Smad2 interaction), zebrafish araf knockdown with mesendoderm phenotype, degradation assay Nature communications High 23591895
2013 PAK4 interacts with Smad2/3 in a kinase-independent manner and blocks TGF-β1-induced phosphorylation of Smad2 at Ser465/467, attenuating Smad2/3 transcriptional activity. Additionally, PAK4 phosphorylates Smad2 on Ser465 in a kinase-dependent manner under HGF stimulation, leading to ubiquitin-proteasome-dependent degradation of Smad2. Co-immunoprecipitation (PAK4-Smad2/3 interaction), kinase assay, dominant-negative and constitutively active PAK4 constructs, ubiquitin-proteasome degradation assay, immunohistochemistry of gastric cancer tissues Oncogene Medium 23934187
2015 Smad2 negatively regulates TGF-β autoinduction in dendritic cells, whereas Smad3 is necessary for robust TGF-β expression. Smad2-deficient DCs expressed higher concentrations of TGF-β and were tolerogenic for colitis models. Smad2-deficient dendritic cells (conditional knockout), TGF-β expression assay, colitis model Immunity Medium 26141582
2016 Smad2 and Smad3 regulate chondrocyte proliferation and differentiation in the growth plate by repressing Ihh expression. Smad2 and Smad3 bind to distinct Smad binding elements (SBEs) in the Ihh promoter, mediating assembly of distinct repressive complexes: TGF-β induces association of Hdac4 with Smad2 (but not Smad3) on the Ihh promoter, while Ski is recruited by Smad3. Cartilage-specific Smad2 conditional KO and global Smad3 KO mice, ChIP analysis of Smad2/3 and Hdac4 on Ihh promoter, SBE mutagenesis, primary chondrocyte TGF-β treatment PLoS genetics High 27741240
2016 Smad3 preferentially localizes to the nucleus in unstimulated cells (sequestered from membrane signaling), while Smad2 remains predominantly cytoplasmic and is a more sensitive TGF-β transducer. The unique linker region of Smad3 impairs its ability to oligomerize with Smad4 upon agonist stimulation. Subcellular fractionation, immunofluorescence localization, Smad4 co-immunoprecipitation assay, ChIP-seq for target gene binding specificity Scientific reports Medium 26905010
2016 Smad2/3 proteins are required for immobilization-induced skeletal muscle atrophy. Immobilization elevates Smad2/3 protein (not mRNA) levels in muscle. Muscle-specific Smad2/3-deficient mice are significantly resistant to denervation-induced atrophy, and expression of atrogenes Atrogin-1 and MuRF1 does not increase in Smad2/3-deficient muscles following denervation. IGF1 signaling inhibits Smad2/3 protein accumulation. Muscle-specific Smad2/3 double knockout mice, denervation/immobilization model, atrogene expression analysis, IGF1 receptor activity assessment The Journal of biological chemistry High 27129272
2017 CCT6A directly binds SMAD2 and suppresses its function, switching TGF-β-induced transcriptional responses from tumor-suppressive (Smad2-dependent) to prometastatic (Smad3-dependent) in NSCLC cells. Co-immunoprecipitation (CCT6A-SMAD2 direct interaction), SMAD2/CCT6A knockdown, transcriptional response assay, NSCLC cell invasion/metastasis assay The Journal of clinical investigation Medium 28375158
2017 Fibroblast-specific deletion of Smad3, but not Smad2, markedly reduces pressure overload-induced cardiac fibrosis. Deletion of Smad2/3 from tissue-resident fibroblasts attenuates injury-induced cellular expansion and expression of fibrosis-mediating genes. Fibroblast- and myofibroblast-specific inducible Cre knockout mice for Smad2 or Smad3, pressure overload model, fibrosis quantification, gene expression analysis The Journal of clinical investigation High 28891814
2018 The crystal structures of SMAD3 in complex with FOXH1 and SMAD2 in complex with corepressor SKI reveal that the MH2 domains of SMAD2 and SMAD3 have multiple hydrophobic patches on their surfaces that serve as cofactor interaction interfaces. Cofactors tether to various subsets of these patches in a cooperative or competitive manner to control TGF-β signaling output. X-ray crystallography of SMAD3-FOXH1 complex and SMAD2-SKI complex, structural analysis of MH2 hydrophobic patches Science signaling High 29588413
2019 Biochemical and structural evidence shows that SMAD2 binding to DNA depends on the conformation of the E3 insert (a structural element unique to SMAD2 previously thought to render SMAD2 unable to bind DNA). SMAD2 remains predominantly cytoplasmic in the basal state and binds SMAD4 upon Nodal TGF-β signaling to join SMAD3:FOXH1 at target promoters. SMAD3 is recruited by FOXH1 to mesendoderm differentiation gene promoters independently of TGF-β signals, while SMAD2 requires signaling. Crystal structure of SMAD2-DNA complex, biochemical DNA binding assay, ChIP-seq for SMAD2 and SMAD3 binding at mesendoderm promoters, SMAD3 and FOXH1 co-IP, mouse mesendoderm differentiation genetic experiments Genes & development High 31582430
2019 WWP2 (E3 ubiquitin ligase, N-terminal isoform) interacts with SMAD2 and mediates TGF-β1-induced nucleocytoplasmic shuttling and transcriptional activity of SMAD2. TGF-β1 stimulation promotes nuclear translocation of WWP2 N-terminal isoforms and their interaction with SMAD2. Co-immunoprecipitation of WWP2-SMAD2, nuclear translocation assay, transgenic mouse with WWP2 N-terminal deletion (reduced cardiac fibrosis), primary cardiac fibroblast assays Nature communications Medium 31399586
2020 SIRT2 directly interacts with and deacetylates SMAD2 at lysine 451, promoting its ubiquitination and degradation. Loss of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) abolishes SIRT2-induced ubiquitination and degradation of SMAD2. SIRT2 also reduces phosphorylation, acetylation and nuclear localization of SMAD2. Co-immunoprecipitation, in vitro deacetylation assay with site identification (K451), ubiquitination assay, SMURF2 knockdown epistasis, conditional Sirt2 KO in renal tubule epithelial cells Cell death & disease High 37777567
2020 LSD1 is recruited together with phosphorylated SMAD2/3 to promoters of TGF-β1-activated and repressed EMT genes within 30-90 minutes of TGF-β1 treatment, triggering a nuclear oxidative wave. This LSD1-pSMAD2/3 complex primes TGF-β1/EMT target genes for activation or repression through targeted DNA oxidation. ChIP (LSD1 and pSMAD2/3 co-recruitment to promoters), confocal microscopy and mass spectrometry for nuclear oxidative wave, co-immunoprecipitation Nucleic acids research Medium 32697292
2020 SMAD2 interacts with MED1 and MED1 downregulation protects SMAD2 from ubiquitin-mediated degradation, stabilizing SMAD2 and promoting TGF-β/SMAD2-dependent EMT and metastasis in cutaneous melanoma. Co-immunoprecipitation (MED1-SMAD2 interaction), ubiquitination assay, MED1 knockdown/overexpression with EMT and migration readouts, in vivo metastasis model The Journal of investigative dermatology Medium 35131256
2021 Creatine promotes cancer metastasis by activating monopolar spindle 1 (MPS1)-mediated phosphorylation of Smad2 and Smad3, leading to upregulation of Snail and Slug expression. MPS1 inhibition suppresses cancer metastasis by downregulating Smad2/3 phosphorylation and downstream Snail/Slug. MPS1 inhibitor treatment, GATM knockdown, Smad2/3 phosphorylation western blot, orthotopic mouse metastasis models Cell metabolism Medium 33811821
2021 In the absence of TGF-β signaling, SMAD2 promotes terminal myogenic differentiation and myogenin expression in a TGF-β receptor-independent manner. Knockout of SMAD2 in primary myoblasts produces smaller myotubes with reduced myogenin expression; loss of Smad2 in satellite cells in vivo results in decreased muscle fiber caliber and impaired regeneration. SMAD2 knockout in primary myoblasts, SMAD2 overexpression (signaling-independent constructs), in vivo satellite cell-specific Smad2 KO, muscle regeneration assay Development (Cambridge, England) Medium 33462116
2021 Mitochondrial dysfunction induces MAPKs-mediated phosphorylation of SMAD2 at a mitochondrial localization, leading to enhanced ALK5-SMAD2 signaling in endothelial cells. Genetic deficiency of SMAD2 prevents retinal vessel growth retardation and arteriovenous malformations in mitochondria-deficient mutant mice. Endothelial-specific SMAD2 KO mice, TFAM/COX10/TRX2 endothelial KO models, ALK5 pharmacological inhibition, SMAD2 phosphorylation localization by cell fractionation Nature communications Medium 36496409
2021 Low fluid shear stress activates Smad2/3 phosphorylation through ALK5 and Neuropilin-1 (which increases sensitivity to BMP-9). Smad2/3 nuclear translocation and target gene expression (but not phosphorylation) are maximal at low FSS and suppressed at physiological high shear. The MEKK3/Klf2 pathway mediates suppression of Smad2/3 nuclear translocation at high FSS through CDK2-dependent phosphorylation of the Smad linker region. EC-specific ALK5 deletion in carotid ligation model, nuclear translocation immunofluorescence, pharmacological CDK2/Klf2 inhibition, in vitro flow chamber experiments Proceedings of the National Academy of Sciences of the United States of America Medium 34504019
2018 Individual phosphorylation sites in the Smad2 linker region (Thr220, Ser245, Ser250, Ser255) are selectively phosphorylated by different kinases (JNK, p38, PI3K for Thr220; multiple kinases for serine residues) in response to thrombin, and are linked to the expression of specific proteoglycan/glycosaminoglycan synthesis genes (XT-1, C4ST-1, CHSY-1). Site-directed mutagenesis of individual linker region residues, selective kinase inhibitors, gene expression analysis for GAG synthesis genes Cellular signalling Medium 30423352
2015 Smad2, but not Smad3, acts as a transcriptional repressor upstream of the BECN1 promoter in endothelial cells, regulating autophagy. Endoglin promotes autophagy by impeding Smad2 transcriptional repressor activity, with Smad2 knockdown directly correlating with enhanced beclin1 levels and autophagy. Smad2 siRNA knockdown, BECN1 promoter reporter assay, endoglin overexpression/knockdown, autophagy quantification The Journal of biological chemistry Medium 25931117
2020 Mutant FOXL2C134W acquires the ability to bind SMAD4 and form a FOXL2C134W/SMAD4/SMAD2/3 complex that binds a novel hybrid DNA motif unique to the mutant. Ablation of SMAD4 or SMAD2/3 strongly reduces FOXL2C134W binding at hybrid sites and decreases expression of associated EMT genes. Co-immunoprecipitation (FOXL2C134W-SMAD4-SMAD2/3 complex), ChIP-seq for hybrid motif binding, siRNA knockdown of SMAD4 and SMAD2/3, chromatin state analysis Cancer research Medium 32641411
2023 PPM1A (protein phosphatase magnesium-dependent 1A) directly interacts with phospho-SMAD2 and acts as a phosphatase for SMAD2. PPM1A knockout protects mice from cartilage degeneration in the DMM model by maintaining higher p-SMAD2 levels in chondrocytes; inhibition of TGF-β/SMAD2 signaling (by SD-208) abolishes the protective phenotype of PPM1A-KO mice. Co-immunoprecipitation (PPM1A-pSMAD2 interaction), PPM1A conditional KO mouse with DMM model, pharmacological rescue with SD-208 (TGF-β/SMAD2 inhibitor), PPM1A pharmacological inhibitors (SC, BC-21) JCI insight High 36752205
2024 Thbs1 activates TGF-β-Smad2/3 signaling which induces ATF4 expression; Smad2/3 together with ATF4 modulate the autophagy-lysosomal pathway (ALP) and ubiquitin-proteasome system (UPS) to facilitate muscle atrophy. Myofiber-specific deletion of Smad2 and Smad3 antagonizes Thbs1-induced muscle atrophy. Smad2/Smad3 myofiber-specific double KO mice, Thbs1 transgenic mice, ATF4 KO mice, ALP and UPS activity assays, Thbs1 KO denervation/caloric restriction models Cell reports High 38678560

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. The EMBO journal 943 9311995
1996 MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell 792 8752209
2017 Fibroblast-specific TGF-β-Smad2/3 signaling underlies cardiac fibrosis. The Journal of clinical investigation 772 28891814
1998 SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. Cell 766 9865696
1996 MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell 650 8980228
2009 Smad2 and 3 transcription factors control muscle mass in adulthood. American journal of physiology. Cell physiology 389 19357234
2007 A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. Journal of cellular biochemistry 320 17340614
1996 A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. Genes & development 311 8756346
2010 Smad2 protects against TGF-beta/Smad3-mediated renal fibrosis. Journal of the American Society of Nephrology : JASN 310 20595680
2012 SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer research 276 23139211
1998 Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. Genes & development 250 9620846
2008 Redundant roles of SMAD2 and SMAD3 in ovarian granulosa cells in vivo. Molecular and cellular biology 160 18809571
2015 Smad2 and Smad3 Inversely Regulate TGF-β Autoinduction in Clostridium butyricum-Activated Dendritic Cells. Immunity 156 26141582
1999 Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 142 10535967
1996 Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers. Cancer research 139 8971158
1999 Smad2 and Smad4 gene mutations in hepatocellular carcinoma. Oncogene 137 10490821
2018 A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3. Human mutation 135 29392890
2021 Creatine promotes cancer metastasis through activation of Smad2/3. Cell metabolism 126 33811821
2016 Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification. Scientific reports 103 26905010
2006 The DNA binding activities of Smad2 and Smad3 are regulated by coactivator-mediated acetylation. The Journal of biological chemistry 100 17074756
2007 Endoglin increases eNOS expression by modulating Smad2 protein levels and Smad2-dependent TGF-beta signaling. Journal of cellular physiology 99 17058229
2017 CCT6A suppresses SMAD2 and promotes prometastatic TGF-β signaling. The Journal of clinical investigation 92 28375158
2018 Linc00462 promotes pancreatic cancer invasiveness through the miR-665/TGFBR1-TGFBR2/SMAD2/3 pathway. Cell death & disease 87 29899418
2019 Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-β signaling. Genes & development 79 31582430
2000 TGF-beta receptor expression and smad2 localization are cell density dependent in fibroblasts. Investigative ophthalmology & visual science 72 10634606
2020 CircCDK14 protects against Osteoarthritis by sponging miR-125a-5p and promoting the expression of Smad2. Theranostics 68 32802182
2021 Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling. Proceedings of the National Academy of Sciences of the United States of America 64 34504019
2014 Opposing roles for Smad2 and Smad3 in peritoneal fibrosis in vivo and in vitro. The American journal of pathology 62 24925688
2019 WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling. Nature communications 59 31399586
1997 Expression and mutational analysis of the DCC, DPC4, and MADR2/JV18-1 genes in neuroblastoma. Cancer research 57 9288786
2016 Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy. The Journal of biological chemistry 54 27129272
2016 Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate. PLoS genetics 54 27741240
2014 Physiological and excessive mechanical compression of articular cartilage activates Smad2/3P signaling. Osteoarthritis and cartilage 54 24795273
2013 Oncogenic PAK4 regulates Smad2/3 axis involving gastric tumorigenesis. Oncogene 53 23934187
2000 Cloning and characterization of zebrafish smad2, smad3 and smad4. Gene 53 10767528
1998 Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway. Genomics 49 9503010
2020 Mutant FOXL2C134W Hijacks SMAD4 and SMAD2/3 to Drive Adult Granulosa Cell Tumors. Cancer research 46 32641411
2020 NEAT1/miR-200b-3p/SMAD2 axis promotes progression of melanoma. Aging 46 33202380
2000 Calmodulin differentially modulates Smad1 and Smad2 signaling. The Journal of biological chemistry 46 11007779
2014 Pin1 induction in the fibrotic liver and its roles in TGF-β1 expression and Smad2/3 phosphorylation. Journal of hepatology 43 24530597
2004 Smad2 and Smad3 coordinately regulate craniofacial and endodermal development. Developmental biology 42 15183723
2018 ACVR1C/SMAD2 signaling promotes invasion and growth in retinoblastoma. Oncogene 41 30401983
2012 Cell biology of Smad2/3 linker region phosphorylation in vascular smooth muscle. Clinical and experimental pharmacology & physiology 38 21883378
2020 The Role of SMAD2/3 in Human Embryonic Stem Cells. Frontiers in cell and developmental biology 37 32850796
2019 BMP3 suppresses colon tumorigenesis via ActRIIB/SMAD2-dependent and TAK1/JNK signaling pathways. Journal of experimental & clinical cancer research : CR 37 31665064
2015 HEB associates with PRC2 and SMAD2/3 to regulate developmental fates. Nature communications 37 25775035
2003 Developmental and stage-specific expression of Smad2 and Smad3 in rat testis. Journal of andrology 37 12634305
2020 The role of Smad2 and Smad3 in regulating homeostatic functions of fibroblasts in vitro and in adult mice. Biochimica et biophysica acta. Molecular cell research 36 32179057
2020 MSTN Mutant Promotes Myogenic Differentiation by Increasing Demethylase TET1 Expression via the SMAD2/SMAD3 Pathway. International journal of biological sciences 36 32210722
1997 MAD-related genes on 18q21.1, Smad2 and Smad4, are altered infrequently in esophageal squamous cell carcinoma. Japanese journal of cancer research : Gann 35 9197523
2021 MMP11 promotes the proliferation and progression of breast cancer through stabilizing Smad2 protein. Oncology reports 33 33649832
2020 USP32 promotes tumorigenesis and chemoresistance in gastric carcinoma via upregulation of SMAD2. International journal of biological sciences 33 32226309
2024 Thbs1 regulates skeletal muscle mass in a TGFβ-Smad2/3-ATF4-dependent manner. Cell reports 32 38678560
2020 Targeted DNA oxidation by LSD1-SMAD2/3 primes TGF-β1/ EMT genes for activation or repression. Nucleic acids research 32 32697292
2017 MicroRNA-21 promotes wound healing via the Smad7-Smad2/3-Elastin pathway. Experimental cell research 32 29154818
2024 Helicobacter pylori promotes gastric cancer progression by activating the TGF-β/Smad2/EMT pathway through HKDC1. Cellular and molecular life sciences : CMLS 31 39545942
2007 Expression of PTEN, PPM1A and P-Smad2 in hepatocellular carcinomas and adjacent liver tissues. World journal of gastroenterology 31 17729405
2023 RBM15 silencing promotes ferroptosis by regulating the TGF-β/Smad2 pathway in lung cancer. Environmental toxicology 30 36715115
2019 A TGFBR2/SMAD2/DNMT1/miR-145 negative regulatory loop is responsible for LPS-induced sepsis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 30784922
2015 Endoglin Regulation of Smad2 Function Mediates Beclin1 Expression and Endothelial Autophagy. The Journal of biological chemistry 30 25931117
2019 miR-145-5p attenuates hypertrophic scar via reducing Smad2/Smad3 expression. Biochemical and biophysical research communications 29 31732152
2013 Araf kinase antagonizes Nodal-Smad2 activity in mesendoderm development by directly phosphorylating the Smad2 linker region. Nature communications 29 23591895
2023 Protein phosphatase PPM1A inhibition attenuates osteoarthritis via regulating TGF-β/Smad2 signaling in chondrocytes. JCI insight 28 36752205
2018 GDF11 Modulates Ca2+-Dependent Smad2/3 Signaling to Prevent Cardiomyocyte Hypertrophy. International journal of molecular sciences 28 29783655
2015 TGF-β/Smad2/3 signal pathway involves in U251 cell proliferation and apoptosis. Gene 28 25701598
2013 Smad2 and Smad3 cooperate and antagonize simultaneously in vertebrate neurogenesis. Journal of cell science 28 24105267
2018 miR‑486‑5p is upregulated in osteoarthritis and inhibits chondrocyte proliferation and migration by suppressing SMAD2. Molecular medicine reports 27 29749497
2017 Combined PI3K/Akt and Smad2 Activation Promotes Corneal Endothelial Cell Proliferation. Investigative ophthalmology & visual science 27 28146239
2023 SIRT2 alleviated renal fibrosis by deacetylating SMAD2 and SMAD3 in renal tubular epithelial cells. Cell death & disease 26 37777567
2021 SEPHS1 promotes SMAD2/3/4 expression and hepatocellular carcinoma cells invasion. Experimental hematology & oncology 26 33622411
2020 SP1/TGF‑β1/SMAD2 pathway is involved in angiogenesis during osteogenesis. Molecular medicine reports 26 32016481
2007 Platelets possess functional TGF-beta receptors and Smad2 protein. Platelets 26 17365852
2024 USF1 transcriptionally activates USP14 to drive atherosclerosis by promoting EndMT through NLRC5/Smad2/3 axis. Molecular medicine (Cambridge, Mass.) 24 38424494
2023 BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma. Gastroenterology 24 37739089
2004 Generation of novel conditional and hypomorphic alleles of the Smad2 gene. Genesis (New York, N.Y. : 2000) 24 15452874
2021 Inhibition of Sirt2 Alleviates Fibroblasts Activation and Pulmonary Fibrosis via Smad2/3 Pathway. Frontiers in pharmacology 23 34925016
2018 Individual Smad2 linker region phosphorylation sites determine the expression of proteoglycan and glycosaminoglycan synthesizing genes. Cellular signalling 23 30423352
2001 Somatic alterations of the DPC4 and Madr2 genes in colorectal cancers and relationship to metastasis. International journal of oncology 23 11172591
2001 Analysis of human meningiomas for aberrations of the MADH2, MADH4, APM-1 and DCC tumor suppressor genes on the long arm of chromosome 18. International journal of cancer 23 11304690
2022 Differential effects of Smad2 and Smad3 in regulation of macrophage phenotype and function in the infarcted myocardium. Journal of molecular and cellular cardiology 22 35780861
2013 The use of gene activated matrix to mediate effective SMAD2 gene silencing against hypertrophic scar. Biomaterials 22 24388384
2006 Inhibition of SMAD2 expression prevents murine palatal fusion. Developmental dynamics : an official publication of the American Association of Anatomists 22 16607645
2020 Bovine lactoferrin enhances osteogenesis through Smad2/3 and p38 MAPK activation. Journal of oral biosciences 21 32464258
2020 Tranilast Inhibits Pulmonary Fibrosis by Suppressing TGFβ/SMAD2 Pathway. Drug design, development and therapy 21 33149556
2018 Hydrophobic patches on SMAD2 and SMAD3 determine selective binding to cofactors. Science signaling 21 29588413
1999 Expression and mutational analysis of the MADR2/Smad2 gene in human prostate cancer. The Prostate 21 10420150
2020 Differential Role of Smad2 and Smad3 in the Acquisition of an Endovascular Trophoblast-Like Phenotype and Preeclampsia. Frontiers in endocrinology 20 32733385
2002 No effects of Smad2 (madh2) null mutation on malignant progression of intestinal polyps in Apc(delta716) knockout mice. Cancer research 19 12183405
1997 Smad4 (homolog of human DPC4) and Smad2 (homolog of human JV18-1): candidates for murine lung tumor resistance and suppressor genes. Carcinogenesis 19 9328171
2022 Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature communications 18 36496409
2020 LINC00266-1/miR-548c-3p/SMAD2 feedback loop stimulates the development of osteosarcoma. Cell death & disease 18 32709857
2015 Follistatin-like 1 attenuates differentiation and survival of erythroid cells through Smad2/3 signaling. Biochemical and biophysical research communications 18 26365350
2023 Exosomal circCOL1A1 promotes angiogenesis via recruiting EIF4A3 protein and activating Smad2/3 pathway in colorectal cancer. Molecular medicine (Cambridge, Mass.) 17 37940881
2022 MED1 Downregulation Contributes to TGFβ-Induced Metastasis by Inhibiting SMAD2 Ubiquitination Degradation in Cutaneous Melanoma. The Journal of investigative dermatology 16 35131256
2021 GDF-8 stimulates trophoblast cell invasion by inducing ALK5-SMAD2/3-mediated MMP2 expression. Reproduction (Cambridge, England) 16 34432647
2021 Endometrial PTEN Deficiency Leads to SMAD2/3 Nuclear Translocation. Cancers 16 34638474
2019 Myostatin Increases Smad2 Phosphorylation and Atrogin-1 Expression in Chick Embryonic Myotubes. The journal of poultry science 16 32055218
2009 Atorvastatin Increases Endoglin, SMAD2, Phosphorylated SMAD2/3 and eNOS Expression in ApoE/LDLR Double Knockout Mice. Journal of atherosclerosis and thrombosis 16 19556713
2021 SMAD2 promotes myogenin expression and terminal myogenic differentiation. Development (Cambridge, England) 15 33462116
2018 Dicer deficiency in proximal tubules exacerbates renal injury and tubulointerstitial fibrosis and upregulates Smad2/3. American journal of physiology. Renal physiology 15 30280598

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