Affinage

TGFBR2

TGF-beta receptor type-2 · UniProt P37173

Length
567 aa
Mass
64.6 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TGFBR2 is a transmembrane serine/threonine kinase receptor that serves as the primary signal-transducing receptor for TGF-β family ligands, governing canonical SMAD2/3 phosphorylation as well as non-canonical TRAF6/TAK1/p38 and ERK1/2 pathways across diverse cell types including epithelial, mesenchymal, neural crest, immune, and vascular smooth muscle cells (PMID:21098638, PMID:22326956, PMID:35882447). TGFBR2 surface availability is tightly regulated by USP33-mediated deubiquitination that prevents lysosomal degradation, ITGB5/SNX17-dependent endosomal recycling, NRP1-mediated sequestration at adherens junctions, and PIEZO1-driven autophagy (PMID:37322017, PMID:38729557, PMID:37220183, PMID:39585648). Heterozygous loss-of-function mutations in TGFBR2 cause Loeys-Dietz syndrome and related aortopathies, paradoxically increasing TGF-β signaling in vivo through compensatory upregulation of ligand and alternative receptor pathways, while somatic inactivation in microsatellite-unstable cancers derepresses Cdk4, promotes EMT, and drives metastasis in cooperation with Wnt and Ras pathway activation (PMID:15731757, PMID:16108056, PMID:29282223). Transcription of TGFBR2 is directly activated by GABPA and SOX4/SMARCA4, repressed by MYOCD/PRMT5 and YAP/TAZ/EZH2, and its mRNA is post-transcriptionally targeted by multiple miRNAs including miR-145, miR-9-5p, and miR-7 (PMID:35549739, PMID:33837205, PMID:33995678, PMID:33296708, PMID:25323858).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 High

    The paradox that heterozygous TGFBR2 loss-of-function mutations increase rather than decrease TGF-β signaling in vivo established that receptor haploinsufficiency triggers compensatory pathway activation, fundamentally reframing the pathogenesis of Loeys-Dietz syndrome.

    Evidence Immunohistochemistry for phospho-Smad2 and gene expression analysis in patient tissues carrying TGFBR2 mutations

    PMID:15731757

    Open questions at the time
    • Mechanism of compensatory TGF-β upregulation not defined
    • Cell types responsible for paradoxical signaling not resolved
  2. 2005 High

    Conditional deletion of Tgfbr2 in neural crest cells demonstrated that TGFBR2 is required cell-autonomously for cardiac outflow tract morphogenesis but dispensable for smooth muscle differentiation, separating these developmental functions.

    Evidence Wnt1-Cre conditional knockout mouse with cardiovascular phenotyping

    PMID:16332365

    Open questions at the time
    • Downstream effectors mediating outflow tract septation not identified
    • Whether other TGF-β receptors compensate for smooth muscle specification not tested
  3. 2006 High

    Establishing that TGFBR2 controls epithelial fate during palatal fusion — by driving MEE disappearance through Irf6 — and that its loss causes Cdk4 derepression in MSI colon cancer defined tissue-specific downstream effector programs.

    Evidence Conditional KO in palatal epithelium with Irf6 expression analysis; TGFBR2 reconstitution in HCT116 with Cdk4 kinase assays

    PMID:16108056 PMID:16780827

    Open questions at the time
    • Direct versus indirect regulation of Irf6 by TGFBR2/SMAD not resolved
    • Whether Cdk4 is a direct transcriptional target of SMAD signaling unknown
  4. 2010 High

    Systematic biochemical profiling of nine disease-associated TGFBR2 mutations revealed that distinct alleles differentially perturb receptor stability, internalization, and the SMAD-versus-ERK signaling balance, explaining genotype-phenotype correlations across LDS, MFS2, and TAAD.

    Evidence Quantitative assays of protein turnover, receptor internalization, SMAD phosphorylation, ERK signaling, and transcriptional reporters in cells expressing mutant alleles

    PMID:21098638

    Open questions at the time
    • Structural basis for differential internalization kinetics not determined
    • In vivo validation of Smad/ERK balance hypothesis not performed
  5. 2012 High

    Genetic epistasis experiments revealed that loss of Tgfbr2 in cranial neural crest activates a non-canonical TRAF6/TAK1/p38 pathway through elevated TGF-β2/TβRIII, and that haploinsufficiency of Tgfb2, Tgfbr1, or Tak1 rescued craniofacial defects, ordering the compensatory signaling cascade.

    Evidence Multiple haploinsufficiency rescue crosses in conditional KO mice with immunostaining for pathway components

    PMID:22326956

    Open questions at the time
    • Whether this non-canonical pathway operates in vascular tissue of LDS patients is untested
    • Direct biochemical reconstitution of the compensatory TRAF6/TAK1 cascade not performed
  6. 2013 High

    Multiple studies established that TGFBR2 integrates post-translational glycosylation, lipid metabolism, and exosome cargo composition as downstream functional outputs, broadening the receptor's role beyond classical transcriptional signaling.

    Evidence TGFBR2 reconstitution in MSI cells showing altered β1-integrin sialylation, Notch1 glycosylation via LFNG induction, exosome proteome remodeling, and lipid droplet accumulation in palatal mesenchyme rescued by p38 inhibition

    PMID:23468914 PMID:23975680 PMID:27156840 PMID:28376875

    Open questions at the time
    • Glycosylation targets beyond β1-integrin and Notch1 not cataloged
    • Whether exosome cargo changes are SMAD-dependent or SMAD-independent unknown
  7. 2014 High

    Identification of miR-145 as a physiologically relevant post-transcriptional regulator of TGFBR2 in vascular smooth muscle — validated by knockout mouse showing increased matrix synthesis — established that miRNA control of TGFBR2 has in vivo functional consequences.

    Evidence Luciferase 3'-UTR reporter, miR-145 knockout mouse with angiotensin II infusion fibrosis model

    PMID:25323858

    Open questions at the time
    • Relative contribution of miR-145 versus other TGFBR2-targeting miRNAs in vascular disease not quantified
  8. 2014 High

    Demonstrating that neural Tgfbr2 deletion impairs brain angiogenesis through an altered secretome (reduced VEGFA) and that Tgfbr2 knockdown in Cdh1−/−;Tp53−/− organoids drives metastasis established TGFBR2 as a mediator of paracrine neurovascular and a suppressor of metastatic programs.

    Evidence Foxg1-Cre conditional KO with conditioned medium rescue; shRNA in gastric organoids with in vivo splenic transplantation

    PMID:24990151 PMID:25315765

    Open questions at the time
    • Specific TGFBR2-dependent secreted factors beyond VEGFA that control angiogenesis not fully defined
    • Whether metastasis suppression is SMAD-dependent in gastric organoids not tested
  9. 2017 High

    Compound genetic models showed that Tgfbr2 loss cooperates specifically with Apc and Kras mutations to produce liver metastasis and EMT, establishing the minimal genetic program for colorectal cancer metastasis.

    Evidence Compound conditional mouse models with organoid culture and splenic transplantation for liver metastasis, RNA-seq

    PMID:29282223

    Open questions at the time
    • Whether the EMT program is reversible upon TGFBR2 restoration not tested
    • Contribution of immune evasion versus cell-intrinsic invasion not separated
  10. 2019 High

    Mechanistic dissection of Tgfbr2 loss in Kras-mutant lung revealed a novel Tgfbr2/ERK/SOX2 axis driving squamous cell carcinoma, showing that TGFBR2 normally sustains ERK signaling that represses SOX2.

    Evidence Multiple conditional KO mouse combinations with ERK inhibitor phenocopy experiments

    PMID:31209059

    Open questions at the time
    • Whether this axis operates in human lung SCC not validated
    • Direct ERK-dependent mechanism of SOX2 repression not defined
  11. 2020 High

    Discovery that YAP/TAZ repress TGFBR2 through dual mechanisms — miR-106b-25 cluster post-transcriptionally and EZH2 recruitment epigenetically — and conversely that SOX4/SMARCA4 and GABPA directly activate TGFBR2 transcription, mapped the transcriptional regulatory logic controlling receptor expression.

    Evidence ChIP assays at TGFBR2 promoter, miRNA manipulation, EZH2 inhibition, GABPA knockdown/overexpression with xenograft validation

    PMID:33296708 PMID:33837205 PMID:35549739

    Open questions at the time
    • Relative dominance of activating versus repressive inputs under physiological conditions unknown
    • Whether TGFBR2 transcriptional regulation differs between normal and cancer cells not systematically compared
  12. 2021 High

    CRISPR knockout of TGFBR2 in patient-derived tumor-infiltrating lymphocytes proved it is the essential receptor for TGF-β-mediated immunosuppression of TILs, abolishing SMAD phosphorylation and restoring cytotoxicity.

    Evidence CRISPR/Cas9 KO in primary patient TILs with SMAD phosphorylation, RNA-seq, cytokine and cytotoxicity assays

    PMID:35882447

    Open questions at the time
    • Long-term persistence and safety of TGFBR2-KO TILs in vivo not established
    • Whether other TGF-β superfamily receptors partially compensate in vivo unknown
  13. 2023 High

    Identification of USP33 as a deubiquitinase that stabilizes TGFBR2 at the plasma membrane and NRP1 as a junctional sequesterer that limits TGFBR2 surface signaling defined opposing post-translational mechanisms controlling receptor surface availability.

    Evidence Mass spectrometry identification plus deubiquitination assays for USP33; reciprocal co-IP and endothelial conditional KO for NRP1

    PMID:37220183 PMID:37322017

    Open questions at the time
    • Ubiquitin chain type specificity of USP33 on TGFBR2 not determined
    • Whether NRP1 regulation operates in non-endothelial cells unknown
  14. 2024 High

    Discovery that ITGB5 scaffolds TGFBR2 with the endosomal sorting nexin SNX17 to promote receptor recycling, and that PIEZO1 promotes TGFBR2 autophagy via Rab3C, established two new trafficking pathways that control receptor surface levels.

    Evidence Co-IP of ITGB5-TGFBR2-SNX17 complex with recycling assays and in vivo metastasis; PIEZO1 conditional KO and Yoda1 activation in Marfan syndrome mice

    PMID:38729557 PMID:39585648

    Open questions at the time
    • Structural basis of ITGB5-TGFBR2 interaction not resolved
    • Whether PIEZO1-dependent autophagy of TGFBR2 is selective or involves bulk receptor degradation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the paradoxical increase in TGF-β signaling upon TGFBR2 haploinsufficiency is mechanistically initiated at the molecular level, and how the multiple transcriptional, miRNA, and trafficking regulatory inputs on TGFBR2 are integrated in vivo to set pathway tone, remain unresolved.
  • No unified quantitative model integrating transcriptional, post-transcriptional, and trafficking regulation of TGFBR2
  • Cell-type-specific compensatory receptor mechanisms underlying paradoxical signaling not identified
  • No structural model of full-length TGFBR2 in complex with its trafficking regulators

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 1
Partners
ITGB5NRP1PIEZO1SMAD2SNX17TGFBR1TRAF6USP33

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Heterozygous loss-of-function mutations in TGFBR2 (or TGFBR1) paradoxically result in increased TGF-β signaling in vivo, as evidenced by nuclear enrichment of phosphorylated Smad2 and increased collagen/CTGF expression in tissues from affected individuals, despite the mutant receptors being unable to support TGF-β signal propagation in vitro. Human genetics (heterozygous mutation identification), immunohistochemistry for p-Smad2, gene expression analysis of collagen and CTGF in patient-derived tissues Nature genetics High 15731757
2005 Conditional knockout of Tgfbr2 in neural crest cells (Wnt1-Cre) does not impair smooth muscle differentiation but causes persistent truncus arteriosus and interrupted aortic arch, demonstrating a cell-autonomous role for TGF-β signaling via TGFBR2 in specific cardiovascular morphogenetic events independent of smooth muscle fate specification. Conditional knockout mouse (Cre/lox), histology, immunostaining Developmental biology High 16332365
2006 Cell-autonomous deletion of Tgfbr2 in palatal epithelial cells (Cre/lox) prevents medial edge epithelium (MEE) disappearance during palatal fusion, causing mutant MEE cells to continue proliferating and form cysts, and downregulates Irf6 expression in MEE, placing TGFBR2 upstream of Irf6 in palatal epithelial fate regulation. Conditional knockout mouse (Cre/lox with genetic lineage labeling), immunostaining, gene expression analysis Developmental biology High 16780827
2007 Conditional deletion of Tgfbr2 (or Alk5) in restricted vascular endothelium does not cause arteriovenous malformations resembling HHT, whereas Alk1 deletion does, demonstrating that TGFBR2 is not required for ALK1 signaling in the pathogenesis of hereditary hemorrhagic telangiectasia type 2. Conditional knockout mouse (endothelial-specific Cre), vascular morphogenesis phenotyping, comparison with Alk1 conditional KO Blood High 17911384
2010 Disease-associated TGFBR2 missense mutations (LDS, MFS2, TAAD) have distinct effects on protein stability, receptor internalization, and downstream Smad/ERK signaling; LDS/MFS2 mutations exert dominant-negative effects on Smad phosphorylation and transcriptional activity, whereas the TAAD-associated R460C mutation retains residual Smad signaling, suggesting the balance of Smad vs. ERK signaling defects determines phenotypic severity. Quantitative cell biology assays: protein expression/turnover, receptor internalization, Smad phosphorylation, ERK signaling, transcriptional reporter assays in cells expressing mutant TGFBR2 alleles Journal of cell science High 21098638
2012 Loss of Tgfbr2 in cranial neural crest cells activates a non-canonical TGF-β signaling pathway: elevated TGF-β2 and TβRIII drive a SMAD-independent TRAF6/TAK1/p38 pathway, causing defective palatal mesenchyme proliferation and cleft palate. Haploinsufficiency of Tgfb2, Tgfbr1, or Tak1 rescued the craniofacial defects, establishing epistatic pathway order. Conditional knockout mouse (Cre/lox), genetic epistasis (haploinsufficiency rescue experiments), immunostaining for pathway components, gene expression analysis The Journal of clinical investigation High 22326956
2012 Conditional deletion of Tgfbr2 in hypertrophic chondrocytes delays terminal chondrocyte differentiation and reduces expression of Col10a1, MMP13, osteopontin, VEGF, PECAM1, and Indian hedgehog, demonstrating that TGFBR2 signaling in hypertrophic chondrocytes positively regulates terminal differentiation, angiogenesis of calcified cartilage, and osteogenesis at least partly via Ihh signaling. Conditional knockout mouse (Col10a1-Cre or equivalent), histology, immunostaining, in situ hybridization Matrix biology High 22885149
2013 Reconstituted TGFBR2 signaling in MSI colorectal cancer cells (HCT116) reduces sialylation (~30% decline in ManNAc incorporation) and specifically decreases sialylation of β1-integrin at the cell surface without affecting β1-integrin protein levels or sialyltransferase transcript levels, indicating TGFBR2 modulates post-translational glycosylation of cell surface proteins. Doxycycline-inducible TGFBR2 reconstitution in isogenic cell line, metabolic radiolabeling with tritiated ManNAc, immunoprecipitation of β1-integrin, RT-PCR of sialyltransferases PloS one High 23468914
2013 Inactivation of Tgfbr2 in Osterix-Cre-expressing dental mesenchyme disrupts molar root formation: mutant mice show failure of root elongation, disorganization of Hertwig's epithelial root sheath, impaired odontoblast differentiation (reduced Dspp), reduced osteoclast numbers, and disrupted osteoblast differentiation, demonstrating that mesenchymal TGFBR2 indirectly regulates epithelial HERS behavior during root development. Conditional knockout mouse (Osx-Cre;Tgfbr2fl/fl), micro-CT, immunostaining, K14 lineage marker for HERS Developmental biology High 23933490
2013 Reconstituted TGFBR2 expression in HCT116 MSI colorectal cancer cells upregulates the glycosyltransferase LFNG, which in turn increases N-acetyl-glucosamine incorporation into the Notch1 receptor, linking TGFBR2 signaling to Notch1 glycosylation. Doxycycline-inducible TGFBR2 reconstitution, Glyco-Gene Chip array, RT-PCR validation, dual radiolabeling ([3H]-GlcNAc and [35S]-methionine), immunoprecipitation of Notch1 Cellular signalling High 27156840
2013 miR-655 directly targets the 3'-UTR of both ZEB1 and TGFBR2 mRNAs, suppressing EMT in pancreatic cancer cells; overexpression of miR-655 downregulates TGFBR2 and reverses the mesenchymal phenotype. Luciferase 3'-UTR reporter assay, miRNA overexpression with phenotypic and molecular readouts PloS one Medium 23690952
2013 Tgfbr2 inactivation in Osterix-Cre odontoblast/osteoblast lineage causes aberrant pulp calcification; loss of TGFBR2 in odontoblasts disrupts cellular polarity, reduces predentin, and causes ectopic fibrous matrix calcification obliterating the pulp chamber, with decreased Dsp and increased Dmp1 expression. Conditional knockout mouse (Osx-Cre;Tgfbr2fl/fl), histology, immunohistochemistry Journal of dental research High 25818583
2014 miR-145 directly targets TGFBR2 in vascular smooth muscle cells; miR-143/145 cluster is induced by endothelial cell co-culture and Notch signaling; miR-145 overexpression suppresses TGF-β-dependent extracellular matrix gene expression, while miR-145 knockout mice show increased matrix synthesis and exaggerated fibrotic response to angiotensin II. Luciferase 3'-UTR reporter assay, co-culture assays, miR-145 overexpression/knockout mouse model, Notch receptor-deficient cells, angiotensin II infusion model Circulation research High 25323858
2014 Neural deletion of Tgfbr2 (Foxg1-Cre) impairs brain angiogenesis through an altered secretome: neural cells lacking TGFBR2 show altered expression/distribution of VEGFA, IGF1, IGF2, TGFβ, ID1, THBS2, and ADAMTS1, and conditioned medium from Tgfbr2-KO neural cells causes branching defects in endothelial cells (HUVEC) that are rescued by supplementing VEGFA. Conditional knockout mouse (Foxg1-Cre;Tgfbr2flox/flox), immunostaining, conditioned medium transfer to HUVEC, rescue experiments with growth factor supplementation Human molecular genetics High 24990151
2014 Tgfbr2 shRNA knockdown in Cdh1−/−;Tp53−/− murine gastric organoids induces invasion in vitro and robust metastatic tumorigenicity in vivo upon splenic transplantation, confirming Tgfbr2 as a metastasis suppressor in gastric cancer. Murine primary organoid culture, shRNA knockdown, in vitro invasion assay, in vivo splenic transplantation metastasis model Genome biology High 25315765
2013 TGFBR2 inactivation in MSI colorectal cancer cells alters exosomal protein cargo and modulates cytokine secretion (IL-4, SCF, PDGF-B) in recipient hepatoma cells in a TGFBR2-expression-dependent manner, indicating TGFBR2 signaling shapes exosome-mediated intercellular communication. Doxycycline-inducible TGFBR2 reconstitution, exosome isolation/characterization by EM/nanoparticle tracking/Western blot, mass spectrometry proteomics, Luminex cytokine profiling, confocal microscopy of exosome uptake Cell communication and signaling High 28376875
2006 TGFBR2 inactivation in MSI colon cancers increases cell proliferation and Cdk4 expression; reconstitution of TGFBR2 in HCT116 MSI colon cancer cells decreases proliferation and reduces Cdk4 expression and kinase activity, identifying Cdk4 deregulation as a pathogenic in vivo consequence of TGFBR2 inactivation. TGFBR2 reconstitution in MSI cell line, Cdk4 kinase activity assay, immunostaining of primary colon cancers, proliferation assays International journal of cancer High 16108056
2017 Combined mutation of Apc, Kras, and Tgfbr2 deletion (but not Apc+Kras+Fbxw7) in intestinal epithelial cells drives EMT-like morphology, submucosal invasion, and the highest incidence of liver metastasis in mouse models, establishing that activation of Wnt and Kras with suppression of TGFβ signaling (via Tgfbr2 loss) is sufficient for colorectal cancer metastasis. Compound conditional mouse models, tumor-derived organoid culture, splenic transplantation for liver metastasis, RNA sequencing Cancer research High 29282223
2019 NG2 glia regulate microglial activation and brain innate immunity through TGF-β2/TGFBR2/CX3CR1 signaling; NG2 glia-derived TGF-β2 acts on microglial TGFBR2 to suppress microglial activation, and gain/loss-of-function of TGFBR2 in microglia modulates CX3CR1-mediated immune responses. Diphtheria toxin-mediated NG2 glia ablation, RNA sequencing, gain/loss-of-function studies, co-culture of NG2 glia and microglia, immunohistochemistry, MPTP mouse PD model BMC medicine High 31727112
2019 Loss of Tgfbr2 in Kras-mutant lung epithelium drives predominant lung squamous cell carcinoma development; mechanistically, Tgfbr2 loss reduces phospho-ERK1/2, which upregulates SOX2 (an SCC oncogenic driver), and this cooperates with SMAD4 repression; ERK1/2 inhibition in Smad4/Kras mice phenocopies Tgfbr2 loss, establishing a Tgfbr2/ERK-Smad4/SOX2 signaling axis in SCC formation. Conditional knockout mouse models (multiple combinations), ERK inhibitor treatment, immunostaining, genetic epistasis Cancer research High 31209059
2021 SOX4 directly transcriptionally activates TGFBR2, and forms a complex with the SWI/SNF ATPase SMARCA4 that maintains open chromatin at TGFBR2 regulatory regions; TGFBR2 is required to mediate SOX4-dependent PI3K/Akt signaling in triple-negative breast cancer. ChIP assay, genomic/proteomic analyses, knockdown/rescue experiments, chromatin accessibility assays NPJ breast cancer High 33837205
2020 YAP/TAZ repress TGFBR2 both post-transcriptionally (via miR-106b-25 cluster) and transcriptionally by recruiting the EZH2 epigenetic repressor to the TGFBR2 locus in non-small cell lung cancer cells. Reporter assays, ChIP, miRNA manipulation, EZH2 knockdown/inhibition, gene expression analysis Cancer letters High 33296708
2017 YAP-1 acts as a transcriptional co-activator of TGFBR2 by binding directly to the TGFBR2 promoter through TEADs, increasing TGFBR2 expression and promoting naive T cell differentiation into regulatory T cells (Tregs) in hepatocellular carcinoma. Luciferase reporter assay with TGFBR2 promoter, ChIP-like binding assay, in vitro T cell differentiation assays, flow cytometry Cellular physiology and biochemistry Medium 28472799
2023 USP33 (a deubiquitinase) binds TGFBR2 (identified by mass spectrometry and luciferase complementation assay), deubiquitinates TGFBR2 to prevent its lysosomal degradation, thereby promoting TGFBR2 accumulation at the cell membrane and sustaining TGF-β signaling activation in pancreatic cancer cells. Mass spectrometry, luciferase complementation assay (protein interaction), deubiquitination assay, lysosomal inhibition experiments, membrane fractionation Cell death & disease High 37322017
2023 NRP1 interacts with TGFBR2 at adherens junctions and reduces plasma membrane localization of TGFBR2 and TGF-β signaling; NRP1 knockdown increases proinflammatory cytokines/adhesion molecules and promotes atherosclerosis, identifying NRP1-TGFBR2 interaction as a regulatory mechanism of endothelial TGF-β signaling under flow. Co-immunoprecipitation (NRP1 with TGFBR2 and VE-cadherin), endothelium-specific NRP1 knockout mouse, atherosclerosis mouse model, flow chamber experiments, TGFBR2 membrane localization assays Science signaling High 37220183
2025 PIEZO1 attenuates TGF-β signaling by promoting endocytosis and autophagy of TGFBR2 mediated by Rab GTPase 3C; PIEZO1 conditional knockout in vascular smooth muscle cells exacerbates TGF-β pathway activation and aortic aneurysm in Marfan syndrome mice, while pharmacological PIEZO1 activation (Yoda1) reverses this, demonstrating PIEZO1 as a negative regulator of TGFBR2 surface availability. Conditional knockout mouse (PIEZO1 KO in VSMCs of Marfan syndrome mice), Yoda1 pharmacological activation, endocytosis/autophagy assays, bioinformatics European heart journal High 39585648
2024 ITGB5 acts as a scaffold that interacts with both TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing its lysosomal degradation, thereby maintaining TGFBR2 surface distribution and TGFβ signaling in gastric cancer metastasis; TGFβ signaling in turn upregulates ITGB5, creating a positive feedback loop. Co-immunoprecipitation (ITGB5-TGFBR2-SNX17 complex), ITGB5 knockdown, TGFBR2 recycling/degradation assays, in vitro invasion and in vivo metastasis models Cancer letters High 38729557
2021 MYOCD localizes to the TGFBR2 promoter region and recruits the PRMT5/MEP50 epigenetic complex to transcriptionally silence TGFBR2 expression in lung cancer cells, rendering MYOCD-deficient NSCLC cells hyperactivated for TGFBR2/TGFβ signaling and particularly sensitive to TGFBR kinase inhibitors. ChIP (MYOCD at TGFBR2 promoter), PRMT5/MEP50 co-recruitment assay, MYOCD loss-of-function in vivo/in vitro, TGFBR kinase inhibitor sensitivity assays Theranostics High 33995678
2021 CRISPR/Cas9-mediated knockout of TGFBR2 in patient-derived ovarian cancer tumor-infiltrating lymphocytes abolishes TGF-β-induced SMAD phosphorylation, prevents global transcriptional responses to TGF-β, restores pro-inflammatory cytokine secretion, and improves cytotoxicity in the presence of TGF-β, demonstrating that TGFBR2 is the essential receptor for TGF-β-mediated immunosuppression of TILs. CRISPR/Cas9 gene knockout in primary patient TILs, SMAD phosphorylation assay, RNA-seq, cytokine secretion assays, cytotoxicity assays Journal for immunotherapy of cancer High 35882447
2013 miR-9-5p directly targets TGFBR2 (and NOX4), suppressing TGF-β1-dependent myofibroblast transformation; miR-9-5p overexpression abrogates TGF-β1-induced TGFBR2 expression and reduces fibrogenesis in bleomycin-induced lung fibrosis mouse model in vivo. Luciferase 3'-UTR reporter assay, miRNA overexpression/inhibition in vitro and in vivo (mouse bleomycin model), Western blot EMBO reports High 26315535
2019 GDF15-induced apoptosis and cytotoxicity in A549 lung cancer cells is dependent on TGFBR2 expression; TGFBR2 knockdown inhibits GDF15-induced caspase-9/caspase-3 activation and reverses GDF15-mediated inhibition of ERK1/2 and p38MAPK phosphorylation, placing TGFBR2 as a required receptor for GDF15-induced apoptotic signaling. siRNA knockdown of TGFBR2, GDF15 overexpression, flow cytometry (annexin V/PI), caspase activation assay, Western blot for ERK/p38 phosphorylation Cell biochemistry and function Medium 31172564
2013 miR-9-5p (also described as miR-9) targets TGFBR2 3'-UTR and suppresses TGF-β1/Smad signaling in hepatic stellate cells; promoter methylation of miR-9-5p is responsible for its downregulation in liver fibrosis, establishing an epigenetically regulated miR-9-5p/TGFBR2 axis in HSC activation. Luciferase 3'-UTR reporter assay, methylation-specific PCR, in vitro HSC activation assays, in vivo carbon tetrachloride liver fibrosis model Cellular physiology and biochemistry Medium 29073595
2022 GABPA transcription factor directly activates TGFBR2 transcription (identified by ChIP); GABPA depletion reduces TGFBR2 and enhances ccRCC proliferation/invasion, while GABPA overexpression inhibits metastasis in vivo; the oncometabolite L-2-HG epigenetically silences GABPA via DNA methylation, indirectly suppressing TGFBR2 and TGFβ signaling. ChIP assay, siRNA/expression vector manipulation, xenograft mouse model, L-2-HG incubation, methylation analysis, RNA sequencing Journal of experimental & clinical cancer research High 35549739
2018 The circular RNA CDR1as sequesters miR-7, which normally targets TGFBR2 3'-UTR; CDR1as competes with TGFBR2 for miR-7 binding, thereby maintaining TGFBR2 expression and promoting EMT/fibrosis in silica-induced pulmonary fibrosis. Dual luciferase 3'-UTR reporter assay (miR-7/TGFBR2), CDR1as/miR-7 interaction assay, in vivo agomir injection in fibrosis mouse model Toxicological sciences Medium 30202956
2013 Loss of Tgfbr2 in palatal mesenchyme causes lipid droplet accumulation due to reduced lipolysis; treatment with p38 MAPK inhibitor or telmisartan blocks TGFβ-mediated p38 MAPK activation, restores lipid metabolism, and rescues cell proliferation and palatal fusion, linking TGFBR2 signaling to lipid metabolic regulation downstream of p38 MAPK. Conditional knockout mouse, lipid droplet staining, lipolysis assay, p38 MAPK inhibitor and telmisartan treatment in vitro and in vivo, rescue of palatal phenotype Human molecular genetics High 23975680
2021 Enzalutamide decreases TGFBR2 protein expression in osteoblasts through PTH1R-mediated endocytosis; PTH1R blockade rescues TGFBR2 levels in osteoblasts and restores enzalutamide sensitivity in prostate cancer cells co-cultured with osteoblasts, identifying PTH1R-mediated TGFBR2 endocytosis as a mechanism of enzalutamide resistance in the bone microenvironment. Co-culture experiments, PTH1R blockade, TGFBR2 protein level assays, endocytosis assays, in vivo mouse bone metastasis model Cancer letters Medium 34752846

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nature genetics 1288 15731757
2007 ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2. Blood 184 17911384
2016 International Registry of Patients Carrying TGFBR1 or TGFBR2 Mutations: Results of the MAC (Montalcino Aortic Consortium). Circulation. Cardiovascular genetics 156 27879313
2009 Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations. Journal of medical genetics 145 19542084
2006 TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome. Human mutation 144 16799921
2006 Cell autonomous requirement for Tgfbr2 in the disappearance of medial edge epithelium during palatal fusion. Developmental biology 124 16780827
2019 NG2 glia regulate brain innate immunity via TGF-β2/TGFBR2 axis. BMC medicine 114 31727112
2017 Combined Mutation of Apc, Kras, and Tgfbr2 Effectively Drives Metastasis of Intestinal Cancer. Cancer research 111 29282223
2014 Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer. Genome biology 104 25315765
2013 miR-655 Is an EMT-suppressive microRNA targeting ZEB1 and TGFBR2. PloS one 102 23690952
2018 The CDR1as/miR-7/TGFBR2 Axis Modulates EMT in Silica-Induced Pulmonary Fibrosis. Toxicological sciences : an official journal of the Society of Toxicology 98 30202956
2015 miR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2. EMBO reports 93 26315535
2012 Modulation of noncanonical TGF-β signaling prevents cleft palate in Tgfbr2 mutant mice. The Journal of clinical investigation 92 22326956
2018 Linc00462 promotes pancreatic cancer invasiveness through the miR-665/TGFBR1-TGFBR2/SMAD2/3 pathway. Cell death & disease 87 29899418
2006 Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders. Human mutation 85 16791849
2013 Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes in familial cases of bicuspid aortic valve. BMC medical genetics 83 23578328
2005 Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFbeta receptor (Tgfbr2) mutant mice. Developmental biology 79 16332365
2014 MicroRNA miR145 regulates TGFBR2 expression and matrix synthesis in vascular smooth muscle cells. Circulation research 76 25323858
2020 YAP/TAZ and EZH2 synergize to impair tumor suppressor activity of TGFBR2 in non-small cell lung cancer. Cancer letters 74 33296708
2014 MicroRNA-301a promotes migration and invasion by targeting TGFBR2 in human colorectal cancer. Journal of experimental & clinical cancer research : CR 70 25551793
2017 MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2. Cell death & disease 67 28518142
2016 Dual targeting of ANGPT1 and TGFBR2 genes by miR-204 controls angiogenesis in breast cancer. Scientific reports 63 27703260
2013 Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation. Developmental biology 63 23933490
2010 Quantitative analysis of TGFBR2 mutations in Marfan-syndrome-related disorders suggests a correlation between phenotypic severity and Smad signaling activity. Journal of cell science 57 21098638
2019 MiR-145 negatively regulates TGFBR2 signaling responsible for sepsis-induced acute lung injury. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 54 30841464
2017 miRNA-520f Reverses Epithelial-to-Mesenchymal Transition by Targeting ADAM9 and TGFBR2. Cancer research 52 28209612
2020 miR-20a-5p/TGFBR2 Axis Affects Pro-inflammatory Macrophages and Aggravates Liver Fibrosis. Frontiers in oncology 49 32117757
2017 YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 48 28472799
2015 miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2) in Colorectal Cancer. PloS one 48 26061281
2007 Severe aortic and arterial aneurysms associated with a TGFBR2 mutation. Nature clinical practice. Cardiovascular medicine 48 17330129
2018 Lnc-SNHG1 Activates the TGFBR2/SMAD3 and RAB11A/Wnt/β-Catenin Pathway by Sponging MiR-302/372/373/520 in Invasive Pituitary Tumors. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 43 30048990
2012 MicroRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression. Osteoarthritis and cartilage 43 22425884
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2018 The miR-371∼373 Cluster Represses Colon Cancer Initiation and Metastatic Colonization by Inhibiting the TGFBR2/ID1 Signaling Axis. Cancer research 39 29748374
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2008 Absence of TGFBR1 and TGFBR2 mutations in patients with bicuspid aortic valve and aortic dilation. The American journal of cardiology 36 18721526
2017 Epigenetically-Regulated MicroRNA-9-5p Suppresses the Activation of Hepatic Stellate Cells via TGFBR1 and TGFBR2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 29073595
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2018 Attenuation of TGFBR2 expression and tumour progression in prostate cancer involve diverse hypoxia-regulated pathways. Journal of experimental & clinical cancer research : CR 34 29699590
2022 CRISPR-mediated TGFBR2 knockout renders human ovarian cancer tumor-infiltrating lymphocytes resistant to TGF-β signaling. Journal for immunotherapy of cancer 33 35882447
2018 A Neutralizing Aptamer to TGFBR2 and miR-145 Antagonism Rescue Cigarette Smoke- and TGF-β-Mediated CFTR Expression. Molecular therapy : the journal of the American Society of Gene Therapy 33 30595527
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2013 Transforming growth factor beta receptor 2 (TGFBR2) changes sialylation in the microsatellite unstable (MSI) Colorectal cancer cell line HCT116. PloS one 33 23468914
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2017 TGFBR2-dependent alterations of exosomal cargo and functions in DNA mismatch repair-deficient HCT116 colorectal cancer cells. Cell communication and signaling : CCS 31 28376875
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2012 Conditional deletion of Tgfbr2 in hypertrophic chondrocytes delays terminal chondrocyte differentiation. Matrix biology : journal of the International Society for Matrix Biology 30 22885149
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2006 Proliferation and Cdk4 expression in microsatellite unstable colon cancers with TGFBR2 mutations. International journal of cancer 29 16108056
2018 miR-93 Promotes the Growth and Invasion of Prostate Cancer by Upregulating Its Target Genes TGFBR2, ITGB8, and LATS2. Molecular therapy oncolytics 28 30294667
2014 MicroRNA-200b stimulates tumour growth in TGFBR2-null colorectal cancers by negatively regulating p27/kip1. Journal of cellular physiology 28 24151081
2007 Resequencing of genes for transforming growth factor beta1 (TGFB1) type 1 and 2 receptors (TGFBR1, TGFBR2), and association analysis of variants with diabetic nephropathy. BMC medical genetics 28 17319955
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2020 Antisense Oligonucleotide in LNA-Gapmer Design Targeting TGFBR2-A Key Single Gene Target for Safe and Effective Inhibition of TGFβ Signaling. International journal of molecular sciences 27 32178467
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2013 Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice. Human molecular genetics 27 23975680
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2005 Significance of mutations in TGFBR2 and BAX in neoplastic progression and patient outcome in sporadic colorectal tumors with high-frequency microsatellite instability. Cancer genetics and cytogenetics 25 15676142
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2012 TGFBR2 but not SPP1 genotype modulates osteopontin expression in Duchenne muscular dystrophy muscle. The Journal of pathology 23 22431140
2009 Identification of novel FBN1 and TGFBR2 mutations in 65 probands with Marfan syndrome or Marfan-like phenotypes. American journal of medical genetics. Part A 23 19533785
2022 GABPA-activated TGFBR2 transcription inhibits aggressiveness but is epigenetically erased by oncometabolites in renal cell carcinoma. Journal of experimental & clinical cancer research : CR 22 35549739
2016 MicroRNA-9 inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2. Bioscience reports 22 27756824
2022 Decrease of circARID1A retards glioblastoma invasion by modulating miR-370-3p/ TGFBR2 pathway. International journal of biological sciences 21 35982888
2019 MicroRNA-3191 promotes migration and invasion by downregulating TGFBR2 in colorectal cancer. Journal of biochemical and molecular toxicology 21 30770602
2012 Pathway analyses identify TGFBR2 as potential breast cancer susceptibility gene: results from a consortium study among Asians. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20 22539603
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2015 Disruption of Tgfbr2 in odontoblasts leads to aberrant pulp calcification. Journal of dental research 19 25818583
2011 Mutations in TGFBR2 gene cause spontaneous cervical artery dissection. Journal of neurology, neurosurgery, and psychiatry 19 21270064
2011 Association between TGFBR2 gene polymorphism (rs2228048, Asn389Asn) and intracerebral hemorrhage in Korean population. Immunological investigations 19 21609163
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2014 Common variants in TGFBR2 and miR-518 genes are associated with hypertension in the Chinese population. American journal of hypertension 17 24687999
2009 A new sporadic case of early-onset Loeys-Dietz syndrome due to the recurrent mutation p.R528C in the TGFBR2 gene substantiates interindividual clinical variability. Journal of applied genetics 17 19875893
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2023 Exosomes from adipose-derived mesenchymal stem cells improve liver fibrosis by regulating the miR-20a-5p/TGFBR2 axis to affect the p38 MAPK/NF-κB pathway. Cytokine 15 37852157
2021 Enzalutamide-induced and PTH1R-mediated TGFBR2 degradation in osteoblasts confers resistance in prostate cancer bone metastases. Cancer letters 15 34752846
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2013 Dural ectasia in Loeys-Dietz syndrome: comprehensive study of 30 patients with a TGFBR1 or TGFBR2 mutation. Clinical genetics 14 24344637
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