Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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transforming growth factor beta receptor 1(TGFBR1) transforming growth factor beta receptor 1(TGFBR1) Related Genes Homo sapiens
CHROMOSOME 9,
CYTOBAND 9q22,
ENSEMBL_GENE_ID ENSG00000106799,
GENERIF_SUMMARY TGF beta type I receptor mRNA concentration on the surface of human osteoblasts is increased by 1 alpha,25-dihydroxyvitamin D3 due to changes in receptor mRNA stability not associaed with an increase in the rate of gene transcription., present in diabetic foot ulcer, Hypertrophic maturation of chondrocytes in induced by the TGF-beta type I receptors., CD44 interaction with the TGF-betaRI kinase promotes activation of multiple signaling pathways required for ankyrin-membrane interaction, tumor cell migration, and oncogenic events during HA and TGF-beta-mediated metastatic breast tumor progression, elucidation of smad requirement in transforming growth factor-beta type I receptor-induced responses, TGF-beta1 receptor expression in peritoneal fibroblasts was increased by hypoxia or hypoxia plus TGF-beta1, but decreased by TGF-beta1 alone., a C-to-T single-nucleotide polymorphism (C-509T) in the TGF-beta1 gene promoter may be associated with altered gene expression and asthma phenotype, expression values for TGF 1 and its receptors I, II, and III were twice as high in the group of patients with a diagnosis of high-grade lymphomas as in the group of patients diagnosed with low-grade lymphomas, Blocking Smad7 expression by RNA interference inhibits association of GADD34-PP1c complex with TbetaRI., combined production of the immunosuppressants IL-10 and TGF-beta, as well as coexpression of TGF-beta RI and RII (required for cellular response to TGF-beta), may act to down-modulate host anti-Mycobacterium tuberculosis immunity, that an increased TGFbetaRI, transforming growth factor-beta signaling has a role in receptor RI induction by histone deacetylase activity inhibition in breast cancer cells, endogenous IGFBP-3 directly inhibits proliferation of human intestinal smooth muscle cells by activation of TGF-betaRI and Smad2, an effect that is independent of its effect on IGF-I-stimulated growth., sphingosine 1-phosphate receptors and the transforming growth factor beta-type I receptor serine/threonine kinase are essential for activation of Smad3 by lysophospholipids, Mutation in the TGFBR1 gene is associated with carcinomas of the kidney and bladder, Dpr2 binds to the TGFbeta receptors ALK5 and ALK4, and accelerates lysosomal degradation of these receptors, NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-beta type I receptor via Smad7, and induces its ubiquitin-dependent degradation, Bikunin neither decreased expression of TGF-beta receptors (TbetaRI and TbetaRII) in cancer cells nor altered the specific binding of 125I TGF-beta1 to the cells., TGF-beta induces biglycan expression through ALK5 and GADD45beta, Genetic alterations reflecting mismatch repair of TGFBR1 gene do not occur in small bowel carcinoid tumors., IL-6 increases trafficking of TGF-beta1 receptors to non-lipid raft-associated pools resulting in augmented TGF-beta1 Smad signaling, possible role of heterozygous mutation in a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development, The high expressions of TGF-beta1 and TGFbR1 play important roles in spontaneous abortion., the Int7G24A variant of the TGFBR1 gene predisposes to small cell lung cancer risk (meta-analysis), Pituitary cells, which demonstrate reduced expression of dopamine beta2 receptor, also show reduction of TGFbeta1 type I receptor., reports the first molecular analysis of MSSE tumours showing loss of heterozygosity of the MSSE region, with loss of the normal allele, providing the first evidence that MSSE is a tumour suppressor gene, TGFbeta1/ALK5 may alleviate scarring in chronic fibrotic disease., HCV NS5A modulates TGF-beta signaling through interaction with TbetaR-I, Int7G24A variant of transforming growth factor-beta receptor type I is associated with invasive breast cancer, Results of this analysis appear to exclude a role for the TGFBR1- or TGFBR2-mediated pathway effect in Kabuki syndrome., ALK5 plays unique, non-redundant cell-autonomous roles during facial development in K14-Cre transgenic mice., A comprehensive genetic analysis of TGFBR1 was performed in patients with Marfan syndrome or Marfan-related phenotypes., TGF-beta type I receptor kinase has a role in progression of growth and metastasis of mouse mammary carcinoma, Mutations in either TGFBR1 or TGFBR2 predispose patients to aggressive and widespread vascular disease (Loeys-Dietz syndrome), The majority of systemic sclerosis (SSc) fibroblasts exhibit elevated levels of transforming growth factor beta type I receptor (TGFbetaRI)., Synthesis of TGFbeta-1 and type I TGFbeta-receptor increases over time in recipients developing chronic allograft nephropathy., The mRNA expressions of TGFbeta receptor type I (TGFbetaRI) in hMSCs increased with the length of cell culture., Enhances tumor invasion and angiogenesis by stimulating expression of matrix metalloproteinase MMP-9., The expression of TGFbetaR I and TGFbetaR II protein in nasal polyps tissues was significant increased than that in chronic rhinosinusitis tissues., Epac1 inhibits TGFbeta-dependent regulation of cell migration and adhesion through TbetaRI, a distinct BMP and TGFbeta-receptor repertoire may explain the reduced chondrogenic capacity of adipose tissue stromal cells in vitro, common variants in TGFBR1 gene do not strongly influence genetic susceptibility to diabetic nephropathy in an Irish Caucasian population., mRNA codifying for TbetaRI was found in platelets., Our analysis definitely excludes the possibility of the TGFBR1*6A allele increasing the risk of colorectal neoplasia in our sample population., data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer, no evidence to support the hypothesis that TGFBR1*6A is associated with lung cancer., The mRNA expression of TGF-beta R I in keloid was higher than that in hyperplasic scars and normal skin., mutations in the TGFBR1,2 gene may be associated with greater phenotypic heterogeneity than previously reported, ALK5-dependent Smad3 signaling is the responsible pathway inducing CTGF expression., 4 new variants of T beta RI in malignant effusion tumor cells identified; characterization of 2 elements controlling its stability & transcriptional activation; expression of one variant bestowed cancer cells with growth advantage in presence of TGFbeta, The identification of the splice variants T beta RIB and the novel isoform T beta RIIC in man clearly contributes to the growing complexity of the TGF-beta family., the TGFBR1(*)6A variant may be associated with an increased risk of low-risk familial breast cancer and might be a marker for poorly differentiated breast cancer., Somatic acquisition of TGFBR1*6A by epithelial and stromal cells during head and neck and colon cancer development., A highly significant association between the 6Ala allele of TGFBR1 gene and patients with Marfan syndrome is demonstrated for the first time., Pronounced changes in the expression and localization of the TGF-beta receptors Tgfbr1 were noted as mouse lungs progressed through the canalicular, saccular, and alveolar stages of development., The aim of this study was to analyse the profile of TGF-beta1 and the expression of its receptor (TbetaR I, TbetaR II and TbetaR III-betaglycan) genes in IPAH and in secondary forms of pulmonary arterial hypertension [Eisenmenger's syndrome patients]., TGF-beta-mediated activation of the ALK5-Smad 3 pathway plays a role in SHH promoted motility and invasiveness of gastric cancer cells, TGF-beta1, TbetaRI, and TbetaRII loss of expression correlates with differentiation in human oral squamous cell carcinomas, TGF-beta mediates its effects on proteoglycan synthesis in VSMCs via the ALK5/Smad2/3 phosphorylation pathway as well as via the p38 MAP kinase signaling cascade., TGF-beta complexes assemble cooperatively through recruitment of the low-affinity (type I) receptor by the ligand-bound high-affinity (type II) pair., A direct effect of TGF-beta signaling via ALK5 on the regulation of TNF-alpha synthesis in macrophages, TGFBR1*6A may contribute to cancer progression through RhoA activation in a TGF-beta signaling-independent manner, both ALK1 and ALK5 are needed for TGF-beta-induced phosphorylation of intracellular mediators Smad1/5, whereas only ALK5 is essential for TGF-beta1-induced phosphorylation of Smad3, reduced TGF beta R1 expression could contribute to the development of malignant phenotype of non-small cell lung cancer, Transforming growth factor-beta1 protects against pulmonary artery endothelial cell apoptosis via ALK5., T beta RI sumoylation controls responsiveness to TGF-beta, with implications for tumour progression, TGF-beta receptor I kinase has a role in the pathobiology of ineffective hematopoiesis, MT1-MMP-dependent TGFbeta signaling through Alk5 is also required for PGE(2)-induced endothelial cord formation in vitro, and Alk5 kinase activity is required for PGE(2)-induced neovascularization in vivo., The high expression of genes coding TGFbetaRI, TGF-betaRII and TGF-betaRIII receptors in all the polyps and healthy tissues, show readiness to transduction of TGFbeta, ACE and TGFBR1 genes interact in influencing the susceptibility to abdominal aortic aneurysm, The expression of TGF-betaR I increased in CD8+ T cells of oral lichen planus compared to controls., study showed that germline allele-specific expression(ASE)of the TGFBR1 gene is a quantitative trait occuring in 10 to 20% of colorectal cancer (CRC) patients & 1 to 3% of controls; estimates suggest ASE confers a substantially increased risk of CRC, The G-308A TNF-alpha promoter polymorphism is a risk factor for asthma and furthermore suggests that the patients with high producer alleles for TNF-alpha (-308) and TGF-beta (-509) have the highest risk of getting this disease in the Punjabi population., Mutations in TGFBR1 and TGFBR2 rarely cause sporadic BAV., TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6., 177 colorectal cancer patients were genotyped for either the major form of the TGFBR1 receptor gene, homozygous for an internal segment of 9 alanines (9A/9A), or the lesser form, heterozygous for the polymorphism containing 6 alanines (9A/6A)., Mutations and polymorphisms in TGFBR1 and TGFBR2 in patients with Marfan syndrome, Loeys-Dietz syndrome and related disorders are described., Behcets disease cases had lower incidence of TGFBR1(transforming growth factor beta receptor 1) *6A polymorphism compared with controls, 7 different common variants in TGFB1 and TGFBR1 were not associated with an increased risk of bladder cancer, analysis of genetic polymorphisms of transforming growth factor-beta1 and its receptors and colorectal cancer susceptibility, these data are consistent with a role for the activin receptor-like kinase 5 in the progression of idiopathic pulmonary arterial hypertension, TGF-beta1 elevates TbetaRII homodimerization to some degree and strongly enhances TbetaRI.TbetaRII heteromeric complex formation., Bioinformatic and functional analysis of TGFBR1 polymorphisms are reported., Smurf2 promotes trophoblast cell migration and invasion, and this function may involve downregulation of TGF-beta type I receptor., The ACVR2 influenced core 1 mucin-type O-glycosylation differentially, upregulation by ACVR2., There is disregulation in expression of the TGFB1 gene and its receptors as well during isolated Raynaud phenomenon as in systemic sclerosis., Sustained co-cultivation with human placenta-derived MSCs enhances TGFBR1 signaling in human breast epithelial cells, leading to EMT and differentiation., Study shows that there is no association between TGFBR1*6A and breast cancer risk., No substantial support for the hypothesis that the polymorphic variants TGFBR1*6A or Int7G24A contribute to familial colorectal cancer risk., loss of TGFbetaRII in hepatocellular carcinoma triggers activation of the TNF pathway known to be regulated by TGF-beta(1) network, age-related shift in ALK1/ALK5 ratio in murine cartilage and a strong correlation between ALK1 and MMP-13 expression in human cartilage, ALK1 and ALK5 are both essential for correct regulation of VEGF, and that disruption of either pathway leads to disease., we find that germline allele-specific expression of TGFBR1, as assayed in lymphoblastoid and colon epithelial cells of colon cancer patients, is a relatively rare event, Results suggest that the TGFBR1*6A allele does not confer an increased risk of colorectal cancer in the Spanish population., In families w/TGFBR1 mutations, men died younger than women based on Kaplan-Meier survival curves. Women often presented with dissections and aneurysms of arteries other than the ascending thoracic aorta., Elevated serum concentrations of the cytokine TGF-beta1 indicate an increased risk for type 2 diabetes. TGF-beta1 may be upregulated to counterbalance metabolic and immunological disturbances preceding type 2 diabetes., Data show that inhibition of TACE activity or expression enhanced the cell surface TbetaRI levels and TGF-beta-induced Smad3 and Akt activation., Secreted by epithelial cells and macrophages and can cause fibrotic changes in lung tissue, Compared with human fallopian tubes without adhesions or atresias, the expression of TGFbeta1, TGFBR1 and TGFBR2 all increased significantly in adhesion cases., role in activating the nerve growth factor (NGF) system in pancraetic stellate cells (PSC) via TGF-beta., Genetic variations in TGFBR1 associate with abdominal aortic aneurysm in a Dutch population., Study data demonstrates downregulated TGFBR1 expression in psoriatic skin., an association between a TGFBR1 haplotype and risk for non-small-cell lung cancer, Inhibition of transforming growth factor beta receptor I kinase blocks hepatocellular carcinoma growth through neo-angiogenesis regulation., Upon TGF-beta1 stimulation ALK5 phosphorylates Smad2 and 3 with a negative impact on ALK2-Smad1, 5 and 8 signaling in prostate cancer cells., The results suggest that the genetic polymorphisms of IL-4R and TGF-beta1 are associated with the risk of colorectal cancer in a Korean population., TGFBR1*6A/9A polymorphism is associated with cancer susceptibility, increasing the risk of breast and ovarian cancer., two novel mutations in the TGFBR1 and TGFBR2 genes in two patients affected with Loeys-Dietz syndrome (LDS) and showing marked phenotypic variability., Mutations and/or alterations in expression of TGF-beta receptors and loss of Smad 4 are frequent in human ovarian cancers., The Int7G24A variant of transforming growth factor-beta receptor type I represents a risk factor for colorectal cancer in the male Spanish population., elevated mucosal expression in ulcerative colitis, The data suggest that vitamin D fulfillment is prerequisite for the TGF-beta1 genotype in exerting its full effect on the fracture prevalence., Findings reveal a hyperactive TGFbeta-TGFbetaR-Smad2 signaling axis needed to maintain epigenetic silencing of critical EMT genes and breast cancer progression., Using microarray gene expression profiling of human lung tumors, dysregulation of transforming growth factor-beta signaling was identified as an important mediator of tumor invasion., Extracellular matrix-induced transforming growth factor-beta receptor signaling dynamics., Int7G24A is a polymorphism of TGFBR1 that is associated with the susceptibility and distant metastasis of osteosarcoma., Neither genetic variation nor allele-specific expression at TGFBR1 is likely to be a major colorectal cancer risk factor., The detection of GDF9 and TGFbetaR1 at both at the protein and mRNA levels suggests that GDF9 may have functions in human preantral follicles., The aim of this study was to investigate the effect of TGF-beta1 targeting by antisense oligonucleotides on the RNA synthesis and protein expression of TGF-beta isoforms and their receptors in keloid-derived fibroblasts., TGFBR1*6A, a dominant polymorphism of TGFBR1, is associated with increased susceptibility and metastasis spread of osteosarcoma in a Chinese population., Results showed development of gastric carcinoma is accompanied by markedly decreased cytotoxic function of NK cells and by elevated IL-10 and TGF-beta1 serum levels., Data demonstrates the capacity of glucosamine to promote the osteogenic differentiation of human dental pulp stem cells, and the underlying mechanism involves a TGF-beta receptor 1-dependent Smad signal pathway., Single nucleotide polymorphisms in TGFBR-1 is associated with colorectal cancer., Thrombin stimulation of proteoglycan synthesis in vascular smooth muscle is mediated by protease-activated receptor-1 transactivation of the transforming growth factor beta type I receptor., the connective tissue weakness does not relate to mutations in the genes FBN1, TGFBR1 and TGFBR2, Smad7 thus has an additional mode of interaction with TGF-beta family type I receptors not possessed by Smad6, which may play roles in mediating the inhibitory effects unique to Smad7., two alleles in TGFBR1 are not always equally expressed, constituting a subtle quantitative trait that is weakly associated with the risk for colorectal cancer., blocking ALK5 may be useful in blocking the profibrotic effects of TGFbeta in gingival fibroblasts., Following TGF-beta1 treatment, the activity of serine/threonine phosphatase and recruitment of PP2A-Balpha by TbetaRI increased in benign cells, but not in malignant cells. Defective recruitment of PP2A-Balpha by TbetaRI causes TGF-beta1 overexpression in cancer cells., GATA6 plays a crucial role for endothelial cell function and survival, at least in part, by suppressing autocrine TGFbeta expression and ALK5-dependent signaling., Studies indicate that endoglin (CD105) interacts with type I and type II TGF-beta receptors and modulates TGF-beta signaling., TbetaRII alone is able to mediate TGFbeta signaling to ERK1/2 without participation of TbetaRI., Germline allele specific expression of TGFBR1 does not confer an increased risk of colorectal cancer., A haplotype of TGFBR1 is predominantly found in non-small cell lung cancer patients displaying TGFBR1 allelic-specific expression., CD109 regulates TGF-beta receptor endocytosis and degradation to inhibit TGF-beta signaling., ALK-1 and ALK-5 are both expressed by the majority of AML patients. In addition, ALK-5 expression has a significant negative impact on complete remission achievement and long-term survival of patients, dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families with multiple self-healing squamous epithelioma, These results provide evidence that the two TbetaRI, Data indicate that expression of TGF-ss1 and TGF-ssR1 could be used as biological markers of bladder carcinoma., in lung cancer cells, SCUBE3 could serve as an endogenous autocrine and paracrine ligand of TGF-beta type II receptor, which could regulate TGF-beta receptor signaling and modulate EMT and cancer progression, TGF-beta1-induced monocyte migration, requiring ALK5 kinase activity and signalling via PI3K and p38. TGF-beta1-driven monocyte motogenicity is fully functional in diabetic conditions., CD109 release from the cell surface in human keratinocytes regulates TGF-beta receptor expression, TGF-beta signalling and STAT3 activation., TGFBR1 has a specific role in TGFbeta mediated tumor invasion., Data indicate that the addition of a TGF-betaRI kinase inhibitor to the present clinical standard (radiation plus TMZ) has the potential to improve clinical outcome in human glioblastoma., we have proposed that TGF-beta regulates the activation state of the endothelium via two opposing type I receptor/Smad pathways, activin receptor-like kinase (ALK)1 and ALK5--{REVIEW}, TGFBR1 Int7G24A and TGFBR2 G-875A polymorphisms may play important roles in the risk of gastric cardia adenocarcinoma in North China., TGFBR1, TGFBR2, and ACTA2 mutations were found in 4 families with thoracic aortic aneurysms and dissections and predominantly fusiform intracranial aneurysms., The TbetaR-I pre-helix extension is structurally ordered in the unbound form and its flanking prolines are essential for binding., Two polymorphisms of TGFBR1 may confer low-penetrance susceptibility of colorectal cancer risk., atypical protein kinase C isoforms regulate transforming growth factor beta (TGFB) signaling by altering cell surface TGFB receptor trafficking and degradation, Variation in TGFBR1 is associated with dizygotic twinning., No association found for this gene for susceptibility to intracranial aneurysm, A selective inhibitor of the TGFbetaR-I kinase can potentiate radiation responses in glioblastoma by coordinately increasing apoptosis., We have shown that TGF-beta1 expression in gastric tumor tissue with HER2/neu-negative status is of prognostic relevance in gastric cancer., Dominant mutations in this gene cause Ferguson-Smith disease. Review., The balance in signalling through either ALK-1 or ALK-5 regulates leptin expression in mesenchymal stem cells., Gene polymorphisms of TGF-beta1 in 869T > C and PAI-1 4G/5G may affect the susceptibility to IPF in Han ethnicity., Mutations of TGFBR1 are associated with Skin tumors induced by sorafenib., Our study suggests there might be an association between the TGFbeta1 29C>T polymorphism and CVD risk in long-term breast cancer survivors., TGFBR1 as a new candidate prognostic biomarker after acute myocardial infarction, Data suggest that TGF-beta, TGF-betaR1, TGF-betaR2, Smad4, pSmad2/3, and E-cadherin are closely related to tumor-node-metastasis (TNM) stage of colorectal cancer (CRC)., the rs1805110T allele is associated with susceptibility to HBV-related hepatocellular carcinoma in males, TGFBR1 intralocus epistatic interaction as a risk factor for colorectal cancer., promoter methylation may exist in the early stage of esophageal squamous cell carcinoma and play important role in gene silencing, Our results show that USP15 regulates the TGF-beta pathway and is a key factor in glioblastoma pathogenesis, Disease-associated TGFBR1 mutations were found to be inactivating for canonical TGF-beta signaling., a cancer-specific nuclear translocation of TbetaRI; its potential function in regulating nuclear RNA processing, as well as a novel gain-of-function mechanism of TGF-beta signaling in cancer, The Smad7-APC complex links the TGFbeta type I receptor to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFbeta., In patients with aortic dissection and aortic aneurysm, cytoplasmic staining of TGFbeta1 receptor shows aortic wall structures in disarray and intimal disruption., TGF-beta family signaling through Smads is conceptually a simple and linear signaling pathway, driven by sequential phosphorylation, with type II receptors activating type I receptors, which in turn activate R-Smads [review], analysis of evolution of the TGF-beta superfamily and how they signal through a single pair of receptors, known as TbetaR-I and TbetaR-II [review], Results uncover USP4 as an important determinant for crosstalk between TGF-beta/TGF-beta type I receptor and AKT signalling pathways., TGF-beta1 and its receptors including TGF-betaRI and TGF-betaRII are abnormally expressed in the peripheral blood of immune thrombocytopenic purpura patients., USP11 augments TGFbeta signalling by deubiquitylating ALK5., several polymorphisms detected in the TGFbeta1 gene and its receptor associated with benign and malignant breast tumors, a critical negative regulation level of TGF-beta signaling mediated by HILI (human PIWIL2) by its ability to interact with Hsp90 and promote TbetaR degradation, TGFBR1*6A and IVS7+24G>A polymorphisms of TGFBR1 are associated with the susceptibility of cancer, Genotyped five tagging single nucleotide polymorphisms (SNPs) to represent common variants in the whole TGFBR1 gene., ALK5-mediated phosphorylation of DeltaNp63alpha is required for the anti-clonogenic effects of TGFBeta and ectopic expression of ALK5(IKD) mimics these effects., Data indicate that upregulation of TbetaRI (TGFbeta receptor 1) expression by cAMP was dependent on transcription., Rare variants in an adjacent region of chromosome 9q22.3 to known TGFBR1 mutations suggest a digenic or multilocus etiology of multiple self-healing squamous epithelioma (MSSE)., Variation in tagged-SNP rs10739778 was associated with preeclampsia in black women., Overexpression of Dlg5 enhances the degradation of TGFBRI., Data indicate that the activation of MAPK and PI3K pathways resulted in TGF-beta1 signaling by down-regulating Nm23-H1 expression and up-regulating the expression of TbetaRI and TbetaRII, favoring further activation of multiple signaling pathways., High TGFBR-1 expression is associated with metastasis in non-small cell lung cancer., The elevated number of circulating regulatory T cells in patients with transient hypogammaglobulinemia of infancy is not associated with any abnormalities in the genes encoding the TGFBR1 or TGFBR2., TGFBR1 and TGFBR2 mutations do not play a major role in isolated myxomatous valve dystrophy. Screening for FLNA mutations is recommended in familial myxomatous valvular dystrophy, particularly if X-linked inheritance is suspected., The expression of TGFbeta receptors (TGFbetaRI and TGFbetaRII) and FGF2 in the lens epithelium of the MCT mice was stronger than that of the wild-type ddY mice at 4 weeks and weaker than that of the wild-type ddY mice at 15 weeks after birth., We describe two patients with a novel missense mutation in TGFBR1 presenting with highly elevated levels of IgE and severe eczema similar to autosomal-dominant Hyper-IgE syndrome., ACLP stimulates the fibroblast-to-myofibroblast transition by promoting SMA expression via TGFbeta signaling and promoting collagen expression through a TGFbeta receptor-independent pathway., TGFBR1 mutations in patients with dural ectasia in Loeys-Dietz syndrome, Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-beta signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts., Lumican binds ALK5 to promote epithelium wound healing, Findings indicate that tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) was required for the interaction between TGFbeta type I receptor (TbetaRI) and presenilin 1 (PS1)., TbR-I 6A allele and 6A/6A genotype are associated with the ovarian cancer risk., data demonstrate that miR-142-3p influences the proliferation of non-small cell lung cancer cells through repression of TGFbetaR1, We review here the investigations leading to the discovery of loss of function mutations in TGFBR1 that are responsible for the disease, These results suggest that ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-b1/ALK5/Smad2 pathway, and thus plays a crucial role in vascular endothelial cells., genetic testing revealed new mutations in FBN1, TGFbetaR1, TGFbetaR2 and ACTA2 detected in patients with clinical diagnosis of Marfan Syndrome, Loeys-Dietz Syndrome and Thoracic Aortic Aneurysms and Dissections., Data show that tacrolimus-induced NAD(P)H-oxidase 4 (Nox4) expression in by aberrant TGF-beta receptor signalling., the hyaluronan receptor CD44 interacts with both PDGFRbeta and TbetaRI., a case-control study and systematic literature review found that sporadic, but not familial colorectal cancer, was associated with TGFBR1*6A polymorphism., Data suggest that ubiquitin specific peptidase 15 (USP15) may play a role in the pathogenesis of psoriasis through regulating the type I TGFbeta receptor (TbetaR-I)/Smad7 pathway., Characteristic TGFbetaR1 expression pattern in keratoacanthoma can facilitate histopathologic distinction from squamous cell carcinoma., Reduced let-7b might be involved in the pathogenesis of chronic thromboembolic pulmonary hypertension by affecting ET-1 and TGBR1 expression and function of arterial endothelial and smooth muscle cells., Results find little evidence for an association between the TGFBR1*6A allele and colorectal cancer risk in certain families., Chinese Han family a pathogenic mutation (rs111426349, c.1459C >T) (TGFBR1) of familial thoracic aortic aneurysm was confirmed, which result in the amino acid substitution p.R487W., PDGF receptor-alpha promotes TGF-beta signaling in hepatic stellate cells via transcriptional and posttranscriptional regulation of TGF-beta receptors., Mutations in genes such as AKT2, CCNA1, MAP3K4, and TGFBR1, were associated significantly with Epstein-Barr-positive gastric tumors, compared with EBV-negative tumors., TGFbetaR1 signaling as a process dysregulated across HPV-related cancers., Donor rs868 AA genotype was associated with worse clinical course of recurrent hepatitis C and more severe symptoms of hepatitis C and fibrosis during follow-up after liver transplantation., We examined nine exons of transforming growth factor b receptor type 1 (TGFbR1) gene in patients with chronic heart failure with different types of heart remodelling, TGF-betaRI and its mRNA levels were lower in older women than in younger ones. In elderly women, only TGF-betaRIota expression correlated negatively with miRNA-21 expression in PBMCs. Age affects TGF-beta signalling in leukocytes by altering its receptor expression., Treatment with a TGFBR1 kinase inhibitor, endocytosis inhibitors or a lysosome inhibitor, normalized the levels of TGFBR1 and TGFBR2., these findings demonstrate that syntenin may act as an important positive regulator of TGF-b signaling by regulating caveolin-1-mediated internalization of TbRI; thus, providing a novel function for syntenin that is linked to cancer progression, The direct fusion of clathrin-coated and caveolae vesicles during TGF-beta receptor endocytic trafficking, which leads to the formation of the multifunctional sorting device, caveolin-1-positive early endosomes, for TGF-beta receptors., these results revealed no correlation between the normalized expression of TGF-beta2, TGF-betaRI, or TGF-betaRII and EDSS scores, Int7G24A polymorphism of gene TGFBR1 involved in the TGF-beta signaling pathway had a significantly increased risk for cancer development. (Meta-analysis), we showed significantly higher HDAC6 levels in GBM from the patients and further showed evidence supporting TGFbeta receptor signaling pathway as a downstream target of HDAC6 in glioblastoma multiforme, The cancer-driven alteration of WWP1 culminates in excessive TbetaRI degradation and attenuated TGFbeta1 cytostatic signaling, a consequence that could conceivably confer tumorigenic properties to WWP1., Women who carry the TGFBR1*6A allele are at lower risk of developing breast cancer., Blocking TGFBR1 receptor up-regulated p21 expression while inhibiting breast tumor cell growth., Data show that macitentan interferes with the profibrotic action of transforming growth factor-beta (TGF-beta), blocking the endothelin receptor type A (ET-1 receptor) portion of the ET-1/TGF-beta receptor complex., results indicate the critical role of TGF-beta R1/Smad2/3 signaling in carbon nanotube-induced fibrogenesis by upregulating collagen production in lung fibroblasts, MiR-1343 reduces the expression of both TGF-beta receptor 1 and 2 by directly targeting their 3'-UTRs., Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes and transforming growth factor beta receptor 1, the level of TGFBR1 and early osteogenic differentiation were abolished in the DPSCs transfected with siRNA for GnT-V knockdown...GnT-V plays a critical role in the hexosamine-induced activation of TGF-b signaling and osteogenic differentiation, Studies indicate that the transforming growth factor beta receptor I 6A (TbetaR-I 6A) allele was associated with breast cancer risk., miR-181b functions as a tumor suppressor and has an important role in proliferation, chemosensitivity to DDP and metastasis of NSCLC by targeting TGFbetaR1/Smad signaling pathway., Short hairpin-mediated downregulation of either ALK5 or ALK1 resulted in a strong inhibition of TGFbeta-induced chondrogenesis., Data suggest that transient suppression of TGFbeta receptor I (TGFbeta receptor) signaling may improve the outcome of islet transplantation., This paper highlights that targeting the BMP and TGFbeta type I and type II receptors causes a downregulation of XIAP, TAK1, and Id1 leading to cell death of lung cancer cells.,
OMIM_DISEASE Multiple self-healing squamous epithelioma, susceptibility to, Loeys-Dietz syndrome 1,
SP_COMMENT catalytic activity:ATP + [receptor-protein] = ADP + [receptor-protein] phosphate., cofactor:Magnesium or manganese., disease:Defects in TGFBR1 are the cause of aortic aneurysm familial thoracic type 5 (AAT5) [MIM:608967]. Aneurysms and dissections of the aorta usually result from degenerative changes in the aortic wall. Thoracic aortic aneurysms and dissections are primarily associated with a characteristic histologic appearance known as 'medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance., disease:Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 1A (LDS1A) [MIM:609192]; also known as Furlong syndrome or Loeys-Dietz aortic aneurysm syndrome (LDAS). LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree., disease:Defects in TGFBR1 are the cause of Loeys-Dietz syndrome type 2A (LDS2A) [MIM:608967]. LDS2 is an aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients., function:On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for TGF-beta., PTM:Phosphorylated at basal levels in the absence of ligand binding. Activated by multiple phosphorylation, mainly in the GS region., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily., similarity:Contains 1 GS domain., similarity:Contains 1 protein kinase domain., subunit:Interacts with CD109. The unphosphorylated protein interacts with FKBP1A and is stabilized the inactive conformation. Phosphorylation of the GS region abrogates FKBP1A binding. Interacts with SMAD2 when phosphorylated on several residues in the GS region., tissue specificity:Found in all tissues examined, most abundant in placenta and least abundant in brain and heart.,
transforming growth factor beta receptor 2(TGFBR2) transforming growth factor beta receptor 2(TGFBR2) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3p22,
ENSEMBL_GENE_ID ENSG00000163513,
GENERIF_SUMMARY Altogether, these results identify a mechanism by which RhoB antagonizes TGF-beta action through transcriptional down-regulation of AP1 in T beta R-II promoter., treatment with the HDAC inhibitor induces TbetaRII promoter activity by the recruitment of the PCAF protein to the NF-Y complex, interacting with the inverted CCAAT box in the TbetaRII promoter, Overexpression of a dominant negatively acting mutant of TGFBR2 in primitive hemopoietic progenitor cells renders them transiently unresponsive to both autocrine and paracrine TGF-beta signaling and leads to their enhanced survival and proliferation., TGF beta type II receptor mRNA concentration on the surface of human osteoblasts is increased by 1 alpha,25-dihydroxyvitamin D3 due to changes in receptor mRNA stability not associated with an increase in the rate of gene transcription., crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex, present in diabetic foot ulcer, TGFBII receptors were purified and refolded; they have an apparent molecular weight of 14 kDa as by size-exclusion chromatography, data suggest the existence of a further definite subgroup of diffuse-type gastric carcinomas with altered TGFbeta-IIR expression, independent from a mutator phenotype with TGFbeta-IIR gene mutations, Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors.These repeats consisted of (A)10 in the TGF beta RII, (G)8 in the BAX, (A)8 in the CASP1, and (CCA)7 in the APP genes., Coding region microsatellite mutations characteristic of defective mismatch repair Identification of TGFbetaRII coding region microsatellite mutations in vivo implicates this gene in the pathogenesis of human T-LBL/ALL., This protein was expressed locally in the media and adeventitia at injected arterial segments without any significant dissemination to remote areas., TGF-beta2 receptor expression in peritoneal fibroblasts was increased by hypoxia or hypoxia plus TGF-beta1, but decreased by TGF-beta1 alone., The loss of TbetaR-II expression in the primary tumor is associated with clinical stage (P <0.01) and predicts a significantly lower survival rate in renal cell carcinoma patients., Human breast tumors were screened for TGFBR2 mutation and/or altered expression of TGFBR2 protein. TGFBR2 was expressed in the epithelium and stroma of tumors, and was higher in patients having positive lymph nodes and/or negative ER and PR expression., role of a CCAAT box and three GC boxes in the regulation of the TbetaR-II promoters in embryonal carcinoma-differentiated cells, Transforming growth factor beta1 receptor II is downregulated by E1A in adenovirus-infected cells., We observed subsequent loss of type II TGFbeta receptor (TBR2) expression in metastatic renal cell carcinomas [RCC}. We propose that loss of TBR3 is necessary for RCC carcinogenesis, and loss of TBR2 leads to acquisition of a metastatic phenotype., ERT mediates the expression of TGF-beta RII, and the transcriptional inhibition of ets-related transcription factor could be a one of the mechanisms of colonic carcinogenesis, TbetaRII in transgenic mice plays a critical role in maintaining the nondifferentiated character of virgin mammary gland epithelium., expression values for TGF 1 and its receptors I, II, and III were twice as high in the group of patients with a diagnosis of high-grade lymphomas as in the group of patients diagnosed with low-grade lymphomas, TGFBR2 has a role in progression of estrogen receptor-negative breast cancer, each of the five Ets proteins influences the TbetaR-II promoter in a unique manner because of important differences in their biochemical properties or their patterns of cellular expression, NMR analysis of the extracellular domain of the human TGFbeta type II receptor in complex with monomeric TGFbeta3, combined production of the immunosuppressants IL-10 and TGF-beta, as well as coexpression of TGF-beta RI and RII (required for cellular response to TGF-beta), may act to down-modulate host anti-Mycobacterium tuberculosis immunity, an increased TGFbetaRI, Our studies show that RDH12 is associated with retinal dystrophy and encodes an enzyme with a unique, nonredundant role in the photoreceptor cells., The first characterized nonepithelial tumors in hereditary nonpolyposis colorectal cancer seem to carry a limited panel of dna replication errors, including a frameshift at the TGFBR2 gene., thrombin via PAR1 induced the internalization of endoglin and type-II TGF-beta receptor (TbetaRII) but not type-I receptors in human ECs, transforming growth factor beta type II receptor promoter activity and acetylation of Sp1 by recruitment of PCAF/p300 to a Sp1.NF-Y complex are induced by Trichostatin A, possible role of heterozygous mutation in a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development, UV-induced down-regulation of TbetaRII and the concerted over-expression of Smad7 may trigger the inhibition of the TGF-beta-induced phosphorylation of Smad2., Identification of TGFBR2 mutations in Marfan syndrome type II provided the direct evidence of the relation in humans., blockade of TGF-beta after intramuscular transfer of the soluble type II TGF-beta receptor gene suppressed hepatic fibrosis, Repression of type II TGF-beta receptor may act as significant determinant of lung adenocarcinoma invasiveness, an early step in tumor progression toward metastasis., TGFBR2 mutations is associated with deregulation of cdk4 and colon cancer, Identification of a novel TGFBR2 gene mutation in a Korean patient with Loeys-Dietz aortic aneurysm syndrome; no mutation in TGFBR2 gene in 30 patients with classic Marfan's syndrome., prostate cancer cells mediate growth inhibition and differentiation of bone marrow endothelial cells through alteration of TGFbetaRII-mediated signal transduction., changes in TbetaRII levels by EGF are EGF receptor-kinase-dependent and are controlled by signals downstream of MEK1/2, Results of this analysis appear to exclude a role for the TGFBR1- or TGFBR2-mediated pathway effect in Kabuki syndrome., Down-regulation of TbetaRII in dermal cells or up-regulation of TbetaRII in epidermal cells reverses their migratory responses to serum and plasma, respectively., The mutation rate of Poly A site of transforming growth factor-beta1 receptor type II in multiple sites keloid was significant higher than that in single site keloid., reduced transforming growth factor-beta type II receptor expression may play a critical role in determining the malignant phenotype of human adrenocortical carcinoma, levels of TGFbeta-1 and TGFbeta R-2 were increased in the intimal matrices, smooth muscle cells, and macrophages, as well as in endothelial cells of atherosclerotic aorta, Signaling through Tgfbr2 regulates the maintenance of boundaries in the sclerotome and developing axial skeleton in transgenic mice., A comprehensive genetic analysis of TGFBR2 was performed in patients with Marfan syndrome or Marfan-related phenotypes., Mice transgenic for directed expression of a dominant negative TGF beta receptor type II, under the CD4 promoter lacking the CD8 silencer, spontaneously develop features characteristic of primary biliary cirrhosis., Results from this family provides further evidence that mutations in TGFbetaR2 cause a distinct syndrome., Mutations in either TGFBR1 or TGFBR2 predispose patients to aggressive and widespread vascular disease (Loeys-Dietz syndrome), The human TbetaRII overexpressed in highly malignant K-ras-transformed thyroid cell clones is a functional receptor essential for a strong reduction of adhesive & migratory behaviour of these cells., The expression of TGFbetaR I and TGFbetaR II protein in nasal polyps tissues was significant increased than that in chronic rhinosinusitis tissues., epidermal growth factor (EGF)-mediated induction of TbetaRII expression may participate in a synergistic interplay between EGF and TGF-beta signaling pathway, TGF-beta RII was not upregulated in cyclosporine-induced gingival growth in patients after kidney transplantation., Mutated TGFBR2 seems to play an important role in the abrogation of transforming growth factor beta signal transduction in giant cell carcinoma cells., mutations of the amino-acid residues, D55 and E142 of TbetaR-II, resulted in loss of TGF-beta binding and downstream signaling activity, The variant alleles of the promoter polymorphisms, TGFB1 C-509T and TGFBR2 G-875A, were associated with a significantly decreased risk of gastric cancer., These results also indicate that the CSF level assay of TGF-beta1, TbetaR-II and LRG is useful for the diagnosis of patients with INPH, and TGF-beta1, TbetaR-II and LRG may be involved in the pathogenesis of the disease., TGFBR2 mutation is associated with CpG island methylator phenotype-high colorectal cancer and indirectly with RUNX3 methylation, common variants in TGFBR2 gene do not strongly influence genetic susceptibility to diabetic nephropathy in an Irish Caucasian population., Genetic testing revealed in patient with diffuse and rapidly progressing vascular disease a de novo mutation in transforming growth factor receptor 2., data suggest that promoter methylation plays an important role in T beta RII gene silencing and subsequent development of a TGF-beta1-resistant phenotype by some B-cell lymphoma cells, TGF-beta receptor type II and its mRNA were found in platelets., High D-glucose increases L-arginine transport and eNOS expression following TbetaRII activation by TGF-beta1 involving p42/44(mapk) and Smad2 in HUVEC., This review of 5 cases describes patients with musculoskeletal abnormalities and a TGFBR2 mutation in the neonatal period who are subsequently diagnosed with Loeys-Dietz syndrome., TGFBR2 gene is reported to be linked to schizophrenia., Genetic variants of TGFB1 and TGFBR2 genes may contribute to the risk of developing gastric cancer., the defective TGFBR2 expression might contribute to the carcinogenesis and/or development of large cell carcinoma, Sequential cytoplasmic truncations resulted in receptor missorting to apical surfaces, and they indicated an essential targeting element(s) near the receptor's C terminus., TGF-beta signaling in reactive stroma is angiogenic and tumor promoting and is mediated in part through a TbetaRII/Smad3-dependent upregulation of FGF-2 expression and release., mutations in the TGFBR1,2 gene may be associated with greater phenotypic heterogeneity than previously reported, RANTES signaling is required for invasion in TGFbetaRII-deficient neoplastic cells., Alterations in TGF-betaRII, BAX, IGFIIR, caspase-5, hMSH3 and hMSH6 genes of microsatellite instability are rare in urinary bladder carcinoma and they are not associated with microsatellite instability or the presence of p53 mutations., it was observed the progression of premalignant lung lesions toward carcinoma in situ is accompanied by a decrease in TBR II expression and apoptosis and an increase in the expression of Ki-67 and MC, genetic variants in transforming growth factor beta receptor II may modulate the risk of esophageal squamous cell carcinoma, TGF-beta receptor 2 downregulation in tumor-associated stroma is associated with colon carcinoma, The identification of the splice variants T beta RIB and the novel isoform T beta RIIC in man clearly contributes to the growing complexity of the TGF-beta family., Mutant p53 attenuates TGF-beta1 signaling. This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus., Mutations at the mononucleotide repeats within the TGF-betaRII gene occurred in certain basal cell carcinomas, not always in association with microsatellite instability ., Both genomic instability and clonal selection of transforming growth factor beta resistant cells contribute to the high frequency of TGFBR2 mutations in microsatellite unstable colon cancer., TGFbeta2 and TbetaRII have roles in the antiestrogenic activity of tamoxifen metabolites in breast cancer, IL-1beta decreases TbetaRII expression by inducing Sp3 via NFkappaB, Molecular genetic analysis demonstrated a heterozygous missense mutation of the transforming growth factor-beta receptor II gene in both the patient and his father, which thus caused Loeys-Dietz syndrome., sequencing of exon 4 of the transforming growth factor-beta receptor type II gene, which showed a band shift by single-strand conformation polymorphism, disclosed a single nucleotide polymorphism, The aim of this study was to analyse the profile of TGF-beta1 and the expression of its receptor (TbetaR I, TbetaR II and TbetaR III-betaglycan) genes in IPAH and in secondary forms of pulmonary arterial hypertension [Eisenmenger's syndrome patients]., KSHV evades both the antiproliferative effects of TGF-beta signaling by silencing TbetaRII gene expression and immune recognition by suppressing TGF-beta-responsive immune cells through the elevated secretion of TGF-beta1, TGF-beta1, TbetaRI, and TbetaRII loss of expression correlates with differentiation in human oral squamous cell carcinomas, TGF-beta complexes assemble cooperatively through recruitment of the low-affinity (type I) receptor by the ligand-bound high-affinity (type II) pair., TGFBR2 mutations are not a major factor in spontaneous spinal CSF leaks., Filtering bleb scarring is associated with an abundant expression of TGF-beta receptors in activated fibroblasts and the deposition of the fibrogenic ED-A fibronectin splice-variant., Cancer-associated missense mutations of the T beta RII gene (TGFBR2) are associated with at least two different phenotypes., The exogenous tTGFbetaRII can efficiently trap TGF-beta I from access to wild-type receptors and can suppress TGF-beta I triggered signals. Thus it may potentially be clinically applied to scar therapy., Mesenchymal stem cells from patients with osteoarthritis showed significantly increased total TGF-beta, TGF-beta1 isoform, TBR-II, and TBR-III mRNA expression compared to controls., mature human M2 macrophages made permissive to TGF-beta by glucocorticoid-induced surface expression of TGF-betaRII activate in response to TGF-beta1, A significant elevation in expression of TGFBR2 in oral squamous cell carcinoma cells was seen in carbon and neon-irradiated cells., The high expression of genes coding TGFbetaRI, TGF-betaRII and TGF-betaRIII receptors in all the polyps and healthy tissues, show readiness to transduction of TGFbeta, The roles played by the ecto/transmembrane (ecto/TM) domains and endodomains of RI and RII TGF-beta receptors in these processes by transfecting 293 or HeLa cells with different combinations of receptor mutants, was analysed., the expression levels of TbetaRII and Smad2 in Sertoli Cell-Only Syndrome testes were upregulated compared to that in the normal controls., The expression level of TGF-betaR II in CD8+ T cells of oral lichen planus did not increase compared with the controls., Mutations in TGFBR1 and TGFBR2 rarely cause sporadic BAV., the frequent loss of stromal TGF-beta type II receptor expression in prostate cancer can relieve the paracrine suppression of Wnt3a expression, Mutations and polymorphisms in TGFBR1 and TGFBR2 in patients with Marfan syndrome, Loeys-Dietz syndrome and related disorders are described., DHT decreases the level of TGF-beta receptor II (TbetaRII) through a transcriptional mechanism., The -1 bp frameshift mutation rates of TGFBR2 and ACVR2 microsatellite sequences are dependent upon the human DNA Mismatch repair background, report of somatic mosaicism of a TGFBR2 missense mutation, c.1336G>A (D446N)in a patient with Loeys-Dietz syndrome; DNA from leukocytes, buccal cells, hair root cells, & nails in the father indicated 52%, 25%, 0%, & 35% of cells harbored the mutation, sTbetaRII attenuates the biological activities of TGF-beta in colorectal cancer, the TGFbeta pathway activation leads to recruitment of a KLF14-mSin3A-HDAC2 repressor complex to the TGFbetaRII promoter, as well as the remodeling of chromatin to increase histone marks that associate with transcriptional silencing., TGF-beta1 elevates TbetaRII homodimerization to some degree and strongly enhances TbetaRI.TbetaRII heteromeric complex formation., High-affinity binding of TGF-beta1/3 to TGF-betaRII is primarily due to hydrogen bonding between Arg25 and 94 of TGF-beta1/3, and Glu119 and Asp32 of TbetaR-II. Arg25 and 94 are substituted by Lys in TGF-beta2, which binds with low affinity to TbetaR-II., hENT1 is down-regulated by activation of TbetaRII by TGF-beta1 in endothelium from umbilical veins., The TGFBR2 presence reduced binding of probes specific for a core substitution and increased branch length in N-glycosylation, even reaching a P-value of 0.0016., Data show that co-expressing constitutively active type I and type II receptors resulted in the phosphorylation of both R-Smad subclasses in a ligand-independent manner., These results indicate that the extracellular domain of TbetaRII mediates receptor partitioning into membrane rafts and efficient entrance into caveolin-positive endosomes., Critical role of type II receptors in balancing BMP9 signaling via ALK1 and emphasize the essential role for BMPR-II in a subset of BMP9 responses in pulmonary artery endothelial cells., 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with chronic kidney disease in low-risk individuals., loss of TGFbetaRII in hepatocellular carcinoma triggers activation of the TNF pathway known to be regulated by TGF-beta(1) network, The four most frequently mutated genes in colorectal cancers with microsatellite instability were ACVR2 (92%), TAF1B (84%), ASTE1/HT001 (80%) and TGFBR2 (77%)., Out of 41 probands with Marfan syndrome, six were identified to have novel TGFBR2 mutations (one frameshift and five missense mutations)., Low expression of Smad4 and TbetaRII may promote metastasis of oral squamous cell carcinoma., Individuals with TGFBR2 mutations are more likely to dissect at aortic diameters <5.0 cm than individuals with TGFBR1 mutations., TGFbetaR2 hypermethylation is associated with multiple myeloma., polymorphism in TGFBR2 are associated with altered secretion of OPN, supporting a role for transforming growth factor beta in OPN production., TGF-betaRII expression was related with depth of invasion, lymph node metastasis, tumor differentiation, and Lauren classification of gastric cancer., Compared with human fallopian tubes without adhesions or atresias, the expression of TGFbeta1, TGFBR1 and TGFBR2 all increased significantly in adhesion cases., Genetic variations in TGFBR2 associate with abdominal aortic aneurysm in a Dutch population., These data show that trichostatin a induces the expression of TbetaR-II mRNA and activates the TbetaR-II promoter in retinoblastoma cells., two novel mutations in the TGFBR1 and TGFBR2 genes in two patients affected with Loeys-Dietz syndrome (LDS) and showing marked phenotypic variability., We show differences in expression of glycosaminoglycans are related to the over-expression of TGF-beta and TGF-betaRII in cultured fibroblasts from hereditary gingival fibromatosis and gingival fibroblasts treated with CyA., TGF-betaRII protein analysis in tumour cells could be introduced in clinical practice as additional prognostic biomarker in HER2-negative breast cancer., Mutations and/or alterations in expression of TGF-beta receptors and loss of Smad 4 are frequent in human ovarian cancers., Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression, The researchers found an association between a common TGFRB2 polymorphism and the risk of sudden cardiac arrest coupled with ventricular arrhythmias in the presence of coronary artery disease., Clinical outcomes appear similar between treated patients with TGFBR2 mutations and individuals with FBN1 mutations in Marfan syndrome and related disorders., Data show that exon junction complex (EJC) downstream of a PTC plays an inhibitory role in translation of TGFbetaR2 mRNA., Low TbetaR-II protein level is due to augmented ubiquitin-dependent degradation and may be involved in lowering of TGF-beta signaling pathway in renal cell carcinoma., Elf3 amino acid residues within the flanking region, including Trp361, are important for the structural integrity of the protein as well as for the Efl3 DNA binding and transactivation activity., Extracellular matrix-induced transforming growth factor-beta receptor signaling dynamics., a missense mutation of TGFBR2 may have a role in aortic root and pulmonary artery aneurysms in a neonate with Loeys-Dietz syndrome type 1B [case report], TGFBR2 forms an endocytic complex with PTH1R in response to PTH and regulates signalling by PTH and TGF-beta. TGFBR2 directly phosphorylates the PTH1R cytoplasmic domain, which modulates PTH-induced endocytosis of the PTH1R-TGFBR2 complex., Mutations of the TGFBR2 gene in Chinese patients with Marfan-related syndrome are reported., The expression of TGF-beta1, its receptor TGFbetaRII, and signaling proteins Smad4 and Smad7 was observed in the majority of colorectal cancer specimens., Mutation in transforming growth factor beta receptor II is associated with colorectal cancer., study presents 2 patients with Loeys-Dietz syndrome with significant skeletal fragility; one was heterozygous for a c.923T > C transition in exon 4 of TGFBR2; the other was heterozygous for a c.1561 T > C transition in exon 7 of TGFBR2, upregulation of the TGFbeta2 level is a common pathological feature of Alzheimer's disease (AD) brains and suggests that it may be closely linked to the development of neuronal death related to AD., Disruption of TGF-beta due to ttranscriptional dysregulation of TGF-beta receptor type II is associated with polyglutamine-induced motor neuron damage in spinal and bulbar muscular atrophy., The aim of this study was to investigate the effect of TGF-beta1 targeting by antisense oligonucleotides on the RNA synthesis and protein expression of TGF-beta isoforms and their receptors in keloid-derived fibroblasts., All 3 SNPs tested were significantly different between nonsegmental vitiligo patients & controls (rs2005061, rs3773645, & rs3773649). Haplotype 1 (CG) and haplotype 2 (GA) of the linkage disequilibrium block were associated with a risk of NSV., TGFbetaRII mutations are relatively late events in the genesis of colorectal cancer with microsatellite instability., Downregulation of TGF beta R-II expression by cigarette smoke-induced Egr-1 may contribute to smoking-induced premature skin aging., TGFBR2 mutations alter smooth muscle cell phenotype and predispose to thoracic aortic aneurysms and dissections., the connective tissue weakness does not relate to mutations in the genes FBN1, TGFBR1 and TGFBR2, miR-21 expression in cord and increased TGFBR2 expression is associated with antenatal IgE production and development of allergic rhinitis, The TGFBR2 metagene(s) showed significant association with a better outcome in ER-positive breast tumors (without stratification by proliferative status) in two of the three data sets., TGFBRII protein expression in benign prostatic hyperplasia is associated with prostate gland volume and with CD4 T-lymphocyte prostatitis., The simultaneous expression of Endoglin (CD105), transforming growth factor (TGF)-beta1 and TGF-beta receptor (R) II were quantified in normal human colon, pre-malignant dysplastic tissue, and invasive colon cancer specimens, The balance between defects in Smad and ERK signaling might be an important determinant of phenotypic severity in disorders related to mutations in TGFBR2., Data suggest a novel mechanism for MEK1 in regulating the sensitivity to TGF-beta signaling by stabilizing TbetaRII., Studies indicate that endoglin (CD105) interacts with type I and type II TGF-beta receptors and modulates TGF-beta signaling., TbetaRII alone is able to mediate TGFbeta signaling to ERK1/2 without participation of TbetaRI., Expression of TssRII mRNA was significantly higher in clear cell adenocarcinoma and mucinous adenocarcinoma, while it was lower in serous adenocarcinoma and endometrioid adenocarcinoma., findings indicate that TGFBR2 gene mutations are responsible for sCAD in 3.6% (95% CI 0.0 to 8.4) of cases., CD109 regulates TGF-beta receptor endocytosis and degradation to inhibit TGF-beta signaling., Case Report, The restoration of the expression of TbetaRII and TbetaRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma., These results provide evidence that the two TbetaRI, Restoration of transforming growth factor-beta receptor II expression in colon cancer cells with microsatellite instability increases metastatic potential in vivo, The synonymous SNP (rs2228048, Asn389Asn) of the TGFBR2 gene was found to be associated with the development of intracerebral hemorrhage in the South Korean population., study concludes that miR-370 is a miRNA that is associated with GC progression by downregulating TGFbeta-RII, Global comparison of gene expression profiles identified 2 striking differences in treated tumors relative to untreated tumors, RNA interference (RNAi) technology was used to silence the expression of TGF-beta receptor, type II (TGFbetaRII) in the LAC cell line, A549, and its effects on cell proliferation, invasion and metastasis were examined., This study provided that TGFR-beta2-875 G/G genotype is a risk factor for brain arteriovenous malformation., Histone deacetylase inhibitor belinostat represses survivin expression through reactivation of transforming growth factor beta (TGFbeta) receptor II leading to cancer cell death, TGFBR1 Int7G24A and TGFBR2 G-875A polymorphisms may play important roles in the risk of gastric cardia adenocarcinoma in North China., in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in Marfan syndrome., TGFBR1, TGFBR2, and ACTA2 mutations were found in 4 families with thoracic aortic aneurysms and dissections and predominantly fusiform intracranial aneurysms., This study suggests that two common genetic polymorphisms in TGFBR2 are associated with the risk of developing abdominal aortic aneurysm, atypical protein kinase C isoforms regulate transforming growth factor beta (TGFB) signaling by altering cell surface TGFB receptor trafficking and degradation, TGFBR2 mutations are not associated with the microsatellite instability-high colorectal cancer., The evidence suggests that TGFBR1 and TGFBR2 are not susceptibility genes for intracranial aneurysm in this population, Results suggest a mechanism for the downregulation of TbetaRII in lung cancer., miR-21 plays an important role in regulating stemness by modulating TGFbetaR2 signaling in colon cancer cells., a novel gain-of-function TbetaRII mutation enhances TGF-beta signaling, leading to more invasive phenotypic changes in human OSCC, report on two LDS patients with mutations in TGFBR2. It appears that LDS can be associated with low bone mass and high bone turnover but increased matrix mineralization of trabecular bone, A novel missense TGFBR2 mutation p.V453E (c.1358T>A) in the proband and two relatives of a Chinese family is associated with a type 2 Marfan syndrome., Data suggest that TGF-beta, TGF-betaR1, TGF-betaR2, Smad4, pSmad2/3, and E-cadherin are closely related to tumor-node-metastasis (TNM) stage of colorectal cancer (CRC)., the rs1805110T allele is associated with susceptibility to HBV-related hepatocellular carcinoma in males, Report down-regulation of TGFBR2 in human abdominal aortic aneurysms., promoter methylation may exist in the early stage of esophageal squamous cell carcinoma and play important role in gene silencing, The abnormal expression of ALK1 and TGFbR2 were found to be independent contributors to nasopharyngeal carcinogenesis., reduced TGF-beta-RII expression in human non-small cell lung cancer is a negative prognostic marker associated with more aggressive tumor behavior and worse clinical outcome, The molecular mechanism that controls TssRII fate in IL-1ss treated cells, was investigated., TGFBR2 but not SPP1 genotype modulates osteopontin expression in Duchenne muscular dystrophy muscle., Single nucleotide polymorphism in TGFBR2 is associated with breast cancer., N-linked glycosylation is essentially required for the suGFccessful cell surface transportation of TGFbetaRII, suggesting a novel mechanism by which the TGF-beta sensitivity can be regulated by N-linked glycosylation levels of TGFbetaRII., Results demonstrate that HES (hairy and enhancer of split), the main transcription factor downstream of Notch, induces strong transactivation of TGF-ssRII by binding the TGF-betaRII promoter through its DNA-binding domain., TGF-beta family signaling through Smads is conceptually a simple and linear signaling pathway, driven by sequential phosphorylation, with type II receptors activating type I receptors, which in turn activate R-Smads [review], analysis of evolution of the TGF-beta superfamily and how they signal through a single pair of receptors, known as TbetaR-I and TbetaR-II [review], Data indicate that abrogation of TGFbeta signaling through introduction of a dominant negative TGFbeta receptor II (TGFbetaRII) in non-metastatic FETalpha colon cancer cells permits metastasis to distal organs, but does not reduce invasive behavior., miR-590-5p promotes proliferation and invasion in human hepatocellular carcinoma cells by directly targeting TGF-beta RII. [mir-590-5p], We report a 13-year-old girl with Loeys-Dietz syndrome (LDS) caused by a known transforming growth factor beta receptor II (TGFBR2) gene mutation, who developed aortic root dilatation and saccular aneurysm of the internal carotid artery., TGF-beta1 and its receptors including TGF-betaRI and TGF-betaRII are abnormally expressed in the peripheral blood of immune thrombocytopenic purpura patients., a critical negative regulation level of TGF-beta signaling mediated by HILI (human PIWIL2) by its ability to interact with Hsp90 and promote TbetaR degradation, Data indicate that MiR-106a inhibits the expression of transforming growth factor-beta receptor 2 (TGFBR2), leading to increased colorectal cancer (CRC) cell migration and invasion., A transgenic model suggests a role for TGFBR2 signaling in dendritic cells (DCs) to prevent autoimmunity primarily through maintenance of DCs in their immature and tolerogenic state., TGFbetaRIIb expression is a regulatory mechanism for TGFbeta2 signal transduction., The SNP rs764522 of TGFBR2 is associated with increased risk of essential hypertension in the elderly Han Chinese population., MED12 is in part cytoplasmic where it negatively regulates TGF-betaR2 through physical interaction. MED12 suppression therefore results in activation of TGF-betaR signaling, which is both necessary and sufficient for drug resistance., an association between TGF-betaRII-negative tumor and higher risk of metastasis to lungs and bones was verified., association of polymorphisms of the TGFBR2 gene with ossification of the posterior longitudinal ligament was confirmed in this study along with a novel unreported, nucleotide variation in intron 1, There may he abnormal gene expression of TbetaR II in pathological scar epidermis., c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TbetaRII at Lys556 and Lys567., Case Report, Data suggest miR-21 plays a critical role in the production of pro-inflammatory cytokines IFN-gamma and IL-17A in dnTGF-betaRII transgenic mice., IQGAP1 in the tumor microenvironment suppresses TGFBR2 and TGF-beta dependent myofibroblastic differentiation to constrain tumor growth., Variation in transforming growth factor beta receptor 2 tagged-SNP rs6550005 was associated with preeclampsia in white women while variation in rs6550005, rs1346907, and rs877572 was associated with preeclampsia in black women., ZEB1 and TGFBR2 identified as direct targets of miR-655, novel role for miR-211 in the regulation of TGFbetaRII and c-Myc during tumorigenesis being revealed should help to develop anti-head and neck squamous cell carcinoma therapies, Data indicate that the activation of MAPK and PI3K pathways resulted in TGF-beta1 signaling by down-regulating Nm23-H1 expression and up-regulating the expression of TbetaRI and TbetaRII, favoring further activation of multiple signaling pathways., stress induced production of TGF-beta2 by BEC can modify liver allograft function by enhancing the de-differentiation of local epithelial cells., The synonymous single nucleotide polymorphism (rs2228048, Asn389Asn) of the TGFBR2 gene may be associated with development of acute rejection in Korean kidney transplantation recipients., The elevated number of circulating regulatory T cells in patients with transient hypogammaglobulinemia of infancy is not associated with any abnormalities in the genes encoding the TGFBR1 or TGFBR2., oral cancers with TGFBR2 downregulation comprise a different group with more aggressive nature; TGFBR2 transcript levels may be developed as a promising prognostic biomarker, The TGFBR2-875G>A contribution to an early relapse in androgen-deprivation therapy patients supports the involvement of TGFbeta1 pathway in castration-resistant prostate cancer., Mutation of TGF-beta receptor II facilitates human bladder cancer progression through altered TGF-beta1 signaling pathway., The SNP (rs1495592) in TGFBR2 gene may not be associated with development of Kawasaki disease (KD)in children, but it is associated with Ccprpnary artery lesions in children with KD., Results suggest that the AR and miR-21 axis exerts its oncogenic effects in prostate tumors by downregulating TGFBR2, hence inhibiting the tumor-suppressive activity of TGFbeta pathway., The present study evaluated the serum levels of specific metalloproteinases (MMP-2 and MMP-9) and investigated the gene TGFBR in 28 patients with aortic valve disease associated with ascending aortic dilatation., Results show that epigenetic loss of TGFBR2 expression in prostatic fibroblasts, initiated by interactions with Prostate cancer results in the promoter methylation and silencing of DNA damage repair mediators., This study suggests that miR-200b plays a tumour-promoting role by targeting CDKN1B (p27/kip1) in colorectal cancers., TGFBR1 and TGFBR2 mutations do not play a major role in isolated myxomatous valve dystrophy. Screening for FLNA mutations is recommended in familial myxomatous valvular dystrophy, particularly if X-linked inheritance is suspected., he expression of TGFbeta receptors (TGFbetaRI and TGFbetaRII) and FGF2 in the lens epithelium of the MCT mice was stronger than that of the wild-type ddY mice at 4 weeks and weaker than that of the wild-type ddY mice at 15 weeks after birth., these findings demonstrated that c/EBPalpha and c/EBPbeta determine the lineage commitment of hepatoblasts by negatively and positively regulating the expression of a common target gene, TGFBR2, respectively., TGFBR2 expression in cancer-associated fibroblasts is associated with survival outcome in pre-menopausal breast cancer, TGFBR2 mutations in patients with dural ectasia in Loeys-Dietz syndrome, TGFb1 rs1800469 C>T polymorphism was significantly associated with decreased risk of conotruncal heart defects. TGFbetaR2 and VEGF polymorphisms may not play a role in the susceptibility of conotruncal heart defects., Treatment with the anti-oxidant N-acetylcysteine reduces ROS elevation and normalizes TGF-beta signaling and target gene expression., In cerebellar granule cells, TGFbetaRII activates the Akt/mTOR pathway which is mediated by GDF15 and Kv2.1., The present study reports an involvement of miR-93-mediated TGFbR2 down-regulation in NPC aggressiveness, thus giving extended insights into molecular mechanisms underlying cancer aggressiveness., Results suggest that TGFBR2 harbors variants that increase the risk of essential and affect blood pressure homeostasis as well as efficacy of antihypertensive agents in a Chinese population., genetic testing revealed new mutations in FBN1, TGFbetaR1, TGFbetaR2 and ACTA2 detected in patients with clinical diagnosis of Marfan Syndrome, Loeys-Dietz Syndrome and Thoracic Aortic Aneurysms and Dissections., The TGFBR2 aberrant splicing was tumor-specific., The moderate overexpression of TGF-beta1 and TbetaRII mRNA in PTC tissues., PDGF receptor-alpha promotes TGF-beta signaling in hepatic stellate cells via transcriptional and posttranscriptional regulation of TGF-beta receptors., Deep-sequencing of a primary tumor and metastasis from a single patient, and functional validation in culture, reveals that FGFR2 and TGFBR2 act as drivers of gastric cancer in primary and metastasis respectively., we observed the coordinated loss of E-cadherin (CDH1) and transforming growth factor beta receptor II (TGFBR2) in esophageal squamous tumors., Identified a 137-bp region upstream of the transcriptional start site that exhibited high promoter activity and was repressed 60% by UV irradiation, where all other TbetaRII promoter constructs exhibited either low promoter activities or no regulation by UV., Results show that metastatic differentiation and genetic heterogeneity of diffuse gastric cancer and reveal the potential metastatic role of TGFBR2 loss-of-function., Regulation of TGFBR2 expression is a direct target of miR145 in vascular smooth muscle cells., There is a possibility of TGFBR2 genetic polymorphism and the risk of cancer development., MicroRNA-19a enhances proliferation of bronchial epithelial cells by targeting TGFbetaR2 gene in severe asthma., The transcriptionl activation of TGFBR2 in CD8+ T lymphocytes is regulated by Kruppel-like factor, KLF10., Furthermore, downregulation of TGFbetaR2 by siRNA showed the same effects on the proliferation and apoptosis as miR-34a mimic in H1299 cells, A cytoplasmic predominant TGF-betaRII expression pattern and a higher pSmad2 expression were associated with decreased breast cancer survival., data indicated that miR-301a correlated with the metastatic and invasive ability in human colorectal cancers and miR-301a exerted its role as oncogene by targeting TGFBR2, Our result suggested that SNP rs6785358 of TGFBR2 gene was associated with increased risk of congenital heart defects in Han Chinese men, these results suggest that simvastatin may inhibit A549 cell proliferation and downregulate TGF-betaRII expression by inhibiting activation of ERK., TGFbeta signaling remains active in some MSI-H CRC cells despite the presence of frameshift mutations in the TGFBR2 gene because the mutated gene still expresses a functional protein., TGF-betaRII and its mRNA levels were lower in older women than in younger ones. Age affects TGF-beta signalling in leukocytes by altering the expression levels of its receptors., Acquisition of low TGFBR2 expression is a contributing factor to endocrine resistance in breast cancer., TGFBR2 variants may have prognostic and predictive value in ER-negative breast cancer patients treated with adjuvant chemotherapy., Our results show that LTBP4 interacts with TGFBR2 and stabilizes TGFbeta receptors by preventing their endocytosis and lysosomal degradation in a ligand-dependent and receptor kinase activity-dependent manner., TGF-beta1 gene C509T polymorphism might be associated with decreased risk of lung adenocarcinoma in Chinese females exposed to cooking oil fumes, but no association was observed TGFBR2 gene G875A polymorphism, In sporadic AAA patients we found one pathogenic (TGFBR2 p.Ile525Phefs*18) and seven VUS, TGFBR2 rs6785358 polymorphism contributes to congenital ventricular septal defect (CVSD) susceptibility, and the G allele may increase the risk of CVSD., these results revealed no correlation between the normalized expression of TGF-beta2, TGF-betaRI, or TGF-betaRII and EDSS scores, Studied folding and crystallization of the type II TGF-beta receptor extracellular domain using the non-detergent sulfobetaine-201, which acts as a pharmacological chaperone., Depletion of IQGAP1 leads to increased TGFBR2 with TGFbeta signaling, explaining in part how reduced IQGAP1 promotes tumor growth, Growth differentiation factor-15 (GDF-15) exhibited TGFBR2-dependent transcriptional upregulation causing increased intracellular and extracellular protein levels in colorectal carcinoma., Ibeta3 co-localized with TGF-beta RII on rigid but not compliant films. Tumor-produced Ibeta3 plays a crucial role in disease progression. Rigid mineralized bone matrix can alter gene expression and bone destruction in an Ibeta3/TGF-beta-dependent manner., TGFbRII expression may be considered a new prognostic factor of diffuse large B cell lymphoma., Case Report, TGFbetaR2 is a potential prognostic tumor biomarker for chemotherapy., we reported a sporadic Japanese case of LDS with a novel TGFBR2 p.Y424H mutation, which appeared to cause pregnancy-related fatal aortic/arterial dissections., TGFBR2 is regulated by an epigenetic auto-feedback regulation in non-small cell lung cancer., Findings suggest that the upregulation of miR-590-5p promotes cellular malignant behavior via the target gene TGFbetaRII in vulvar squamous cell carcinoma., Data (including data from studies in transgenic mice) suggest intraislet pancreatic duct cells are capable of giving rise to insulin-secreting beta-cells; Tgfbr2/transforming growth factor-beta type II receptor appears to involved in this process., TGF-beta2 induces Grb2 to recruit PI3-K to TGF-RII that activates JNK/AP-1-signaling and augments invasiveness of Theileria-transformed macrophages., MiR-1343 reduces the expression of both TGF-beta receptor 1 and 2 by directly targeting their 3'-UTRs., High levels of TbetaRII expression were associated with lymph node metastasis, increasing tumor clinical stage, and poorer 5-year disease-free survival in patients with breast cancer. TbetaRII may be a potential prognostic marker for breast cancer., AT2R downregulates the expression of TGF-betaRII in human proximal tubule cells, This paper highlights that targeting the BMP and TGFbeta type I and type II receptors causes a downregulation of XIAP, TAK1, and Id1 leading to cell death of lung cancer cells.,
OMIM_DISEASE Esophageal cancer, somatic, Loeys-Dietz syndrome 2, Colorectal cancer, hereditary nonpolyposis, type 6,
SP_COMMENT catalytic activity:ATP + [receptor-protein] = ADP + [receptor-protein] phosphate., cofactor:Magnesium or manganese., disease:Defects in TGFBR2 are a cause of esophageal cancer [MIM:133239]., disease:Defects in TGFBR2 are the cause of aortic aneurysm familial thoracic type 3 (AAT3) [MIM:610380]. Aneurysms and dissections of the aorta usually result from degenerative changes in the aortic wall. Thoracic aortic aneurysms and dissections are primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. AAT3 is an autosomal dominant disorder with reduced penetrance and variable expression., disease:Defects in TGFBR2 are the cause of hereditary non-polyposis colorectal cancer type 6 (HNPCC6) [MIM:190182]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. HNPCC6 is a type of colorectal cancer complying with the clinical criteria of HNPCC, except that the onset of cancer was beyond 50 years of age in all cases., disease:Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 1B (LDS1B) [MIM:610168]. LDS1 is an aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by arterial tortuosity and aneurysms, craniosynostosis, hypertelorism, and bifid uvula or cleft palate. Other findings include exotropy, micrognathia and retrognathia, structural brain abnormalities, intellectual deficit, congenital heart disease, translucent skin, joint hyperlaxity and aneurysm with dissection throughout the arterial tree., disease:Defects in TGFBR2 are the cause of Loeys-Dietz syndrome type 2B (LDS2B) [MIM:610380]; formerly Marfan syndrome type 2. LDS2 is an aortic aneurysm syndrome with widespread systemic involvement. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, diffuse arterial aneurysms and dissections, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. LDS2 is characterized by the absence of craniofacial abnormalities with the exception of bifid uvula that can be present in some patients., function:On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for TGF-beta., PTM:Phosphorylated on a Ser/Thr residue in the cytoplasmic domain., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily., similarity:Contains 1 protein kinase domain., subunit:Binds to DAXX. Interacts with TCTEX1D4.,