Genomes and Genes
Gene Symbol: TGFBR2
Description: transforming growth factor beta receptor 2
Alias: AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2, RIIC, TAAD2, TBR-ii, TBRII, TGFR-2, TGFbeta-RII, TGF-beta receptor type-2, TGF-beta receptor type IIB, TGF-beta type II receptor, tbetaR-II, transforming growth factor beta receptor II, transforming growth factor beta receptor type IIC, transforming growth factor, beta receptor II (70/80kDa), transforming growth factor, beta receptor II alpha, transforming growth factor, beta receptor II beta, transforming growth factor, beta receptor II delta, transforming growth factor, beta receptor II epsilon, transforming growth factor, beta receptor II gamma
- LeMaire S, Pannu H, Tran Fadulu V, Carter S, Coselli J, Milewicz D. Severe aortic and arterial aneurysms associated with a TGFBR2 mutation. Nat Clin Pract Cardiovasc Med. 2007;4:167-71 pubmed..Genetic testing also revealed a de novo mutation in transforming growth factor beta receptor 2. Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease. ..
- Mathew S, Murty V, Cheifetz S, George D, Massague J, Chaganti R. Transforming growth factor receptor gene TGFBR2 maps to human chromosome band 3p22. Genomics. 1994;20:114-5 pubmed..In this study, we map the chromosomal position of the gene that encodes the type II receptor of TGF-beta (HGM symbol TGFBR2), a multifunctional regulator of cell proliferation and differentiation...
- Boileau C, Jondeau G, Babron M, Coulon M, Alexandre J, Sakai L, et al. Autosomal dominant Marfan-like connective-tissue disorder with aortic dilation and skeletal anomalies not linked to the fibrillin genes. Am J Hum Genet. 1993;53:46-54 pubmed..39 (for Fib15) and -13.34 (for Fib5), at theta = .001, indicating that the mutation is at a different locus. This phenotype thus represents a new connective-tissue disorder, overlapping but different from classic Marfan syndrome. ..
- Sakai H, Visser R, Ikegawa S, Ito E, Numabe H, Watanabe Y, et al. Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes. Am J Med Genet A. 2006;140:1719-25 pubmedIn order to evaluate the contribution of FBN1, FBN2, TGFBR1, and TGFBR2 mutations to the Marfan syndrome (MFS) phenotype, the four genes were analyzed by direct sequencing in 49 patients with MFS or suspected MFS as a cohort study...
- Passos J, Nelson G, Wang C, Richter T, Simillion C, Proctor C, et al. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol. 2010;6:347 pubmed publisher..and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta. These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR...
- Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, et al. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001;276:12477-80 pubmed..These results thus reveal a novel function of Smad7, i.e. induction of degradation of TbetaR-I through recruitment of an E3 ligase to the receptor. ..
- Akutsu K, Morisaki H, Takeshita S, Sakamoto S, Tamori Y, Yoshimuta T, et al. Phenotypic heterogeneity of Marfan-like connective tissue disorders associated with mutations in the transforming growth factor-beta receptor genes. Circ J. 2007;71:1305-9 pubmed..Among the remaining 11 patients, 1 patient had mutations in TGFBR1, 2 had mutations in TGFBR2, and 1 had mutations in COL3A1...
- Jin G, Deng Y, Miao R, Hu Z, Zhou Y, Tan Y, et al. TGFB1 and TGFBR2 functional polymorphisms and risk of esophageal squamous cell carcinoma: a case-control analysis in a Chinese population. J Cancer Res Clin Oncol. 2008;134:345-51 pubmed..Several functional polymorphisms were identified in TGFB1 and TGFBR2 and associated with elevated serum or plasma level of TGF-beta1 and enhanced transcription activity of TGFBR2...
- Koli K, Arteaga C. Processing of the transforming growth factor beta type I and II receptors. Biosynthesis and ligand-induced regulation. J Biol Chem. 1997;272:6423-7 pubmed..These results show differential processing and turnover of TGFbeta-IR and TGFbeta-IIR providing a potential additional mechanism for modulation of cellular responses to TGFbetas. ..
- Chowdhury S, Howell G, Teggart C, Chowdhury A, Person J, Bowers D, et al. Histone deacetylase inhibitor belinostat represses survivin expression through reactivation of transforming growth factor beta (TGFbeta) receptor II leading to cancer cell death. J Biol Chem. 2011;286:30937-48 pubmed publisher..Therefore, patient populations exhibiting high survivin expression with epigenetically silenced TGF?RII might potentially benefit from the use of this histone deacetylase inhibitor. ..
- Jin Q, Hemminki K, Grzybowska E, Klaes R, Söderberg M, Zientek H, et al. Polymorphisms and haplotype structures in genes for transforming growth factor beta1 and its receptors in familial and unselected breast cancers. Int J Cancer. 2004;112:94-9 pubmed..The possible contribution of 6A/6A homozygosity in the TGF-betaRI gene to breast cancer needs to be confirmed in an independent study. ..
- Garamszegi N, Garamszegi S, Samavarchi Tehrani P, Walford E, Schneiderbauer M, Wrana J, et al. Extracellular matrix-induced transforming growth factor-beta receptor signaling dynamics. Oncogene. 2010;29:2368-80 pubmed publisher..This signaling mechanism expands and partially explains TGF-beta receptor dynamics and consequential signaling diversity-related gene expressional plasticity. ..
- Watanabe Y, Sakai H, Nishimura A, Miyake N, Saitsu H, Mizuguchi T, et al. Paternal somatic mosaicism of a TGFBR2 mutation transmitting to an affected son with Loeys-Dietz syndrome. Am J Med Genet A. 2008;146A:3070-4 pubmed publisherWe report on somatic mosaicism of a TGFBR2 missense mutation, c.1336G>A (D446N). The affected son with the heterozygous mutation was previously reported [Sakai et al. (2006); Am J Med Genet A 140A:1719-1725]...
- Kavsak P, Rasmussen R, Causing C, Bonni S, Zhu H, Thomsen G, et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 2000;6:1365-75 pubmed..These studies thus define Smad7 as an adaptor in an E3 ubiquitin-ligase complex that targets the TGF beta receptor for degradation. ..
- Yetman A, Beroukhim R, Ivy D, Manchester D. Importance of the clinical recognition of Loeys-Dietz syndrome in the neonatal period. Pediatrics. 2007;119:e1199-202 pubmed..patients were initially suspected to have Larsen syndrome or Beals syndrome but were subsequently diagnosed with a TGFBR2 mutation diagnostic of Loeys-Dietz syndrome...
- Jin G, Wang L, Chen W, Hu Z, Zhou Y, Tan Y, et al. Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of gastric cancer in a Chinese population. Int J Cancer. 2007;120:1330-5 pubmed..We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk...
- Mizuguchi T, Collod Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T, et al. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet. 2004;36:855-60 pubmed..Identification of a 3p24.1 chromosomal breakpoint disrupting the gene encoding TGF-beta receptor 2 (TGFBR2) in a Japanese individual with Marfan syndrome led us to consider TGFBR2 as the gene underlying association with ..
- Song K, Wang H, Krebs T, Kim S, Danielpour D. Androgenic control of transforming growth factor-beta signaling in prostate epithelial cells through transcriptional suppression of transforming growth factor-beta receptor II. Cancer Res. 2008;68:8173-82 pubmed publisher..These results provide fresh insight on the mechanism of growth control by androgens and the progression of prostate cancer to androgen independence. [Cancer Res 2008;68(19):8173-82]. ..
- Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science. 1995;268:1336-8 pubmed..RII mutation, by inducing the escape of cells from TGF-beta-mediated growth control, links DNA repair defects with a specific pathway of tumor progression. ..
- Muramatsu Y, Kosho T, Magota M, Yokotsuka T, Ito M, Yasuda A, et al. Progressive aortic root and pulmonary artery aneurysms in a neonate with Loeys-Dietz syndrome type 1B. Am J Med Genet A. 2010;152A:417-21 pubmed publisher..caused by heterozygous mutations of transforming growth factor beta receptor type 1 (TGFBR1) or type 2 (TGFBR2) genes...
- Ki C, Jin D, Chang S, Kim J, Kim J, Park B, et al. 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. Clin Genet. 2005;68:561-3 pubmed
- Wrana J, Attisano L, Carcamo J, Zentella A, Doody J, Laiho M, et al. TGF beta signals through a heteromeric protein kinase receptor complex. Cell. 1992;71:1003-14 pubmed..This mode of operation points to fundamental differences between this receptor and the protein-tyrosine kinase cytokine receptors. ..
- Mincione G, Di Marcantonio M, Artese L, Vianale G, Piccirelli A, Piccirilli M, et al. Loss of expression of TGF-beta1, TbetaRI, and TbetaRII correlates with differentiation in human oral squamous cell carcinomas. Int J Oncol. 2008;32:323-31 pubmed..TGF-beta1 and TGF-beta1 receptor expression significantly decreased as tumors became less differentiated and thus more aggressive, suggesting a functional role of these molecules in oral tumor progression. ..
- Bandyopadhyay B, Han A, Dai J, Fan J, Li Y, Chen M, et al. TbetaRI/Alk5-independent TbetaRII signaling to ERK1/2 in human skin cells according to distinct levels of TbetaRII expression. J Cell Sci. 2011;124:19-24 pubmed publisher..This study provides an explanation for why TGF? selectively activates ERK1/2 in certain cell types and direct evidence for T?RI-independent T?RII signaling to a R-Smad-independent pathway. ..
- Stheneur C, Collod Beroud G, Faivre L, Gouya L, Sultan G, Le Parc J, et al. Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders. Hum Mutat. 2008;29:E284-95 pubmed publisherTGFBR1 and TGFBR2 gene mutations have been associated with Marfan syndrome types 1 and 2, Loeys-Dietz syndrome and isolated familial thoracic aortic aneurysms or dissection...
- Ogino S, Kawasaki T, Ogawa A, Kirkner G, Loda M, Fuchs C. TGFBR2 mutation is correlated with CpG island methylator phenotype in microsatellite instability-high colorectal cancer. Hum Pathol. 2007;38:614-20 pubmedThe transforming growth factor-beta receptor type 2 gene (TGFBR2) is mutated in most microsatellite instability-high (MSI-H) colorectal cancers...
- Munoz Antonia T, Muro Cacho C, Sharma S, Cantor A, Bepler G. Expression of TGFbeta type-II receptor in association with markers of proliferation and apoptosis in premalignant lung lesions. Cancer. 2007;110:1527-31 pubmed..observed that the progression of premalignant 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 MCM2...
- Datta P, Moses H. STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling. Mol Cell Biol. 2000;20:3157-67 pubmed..Thus, we describe a mechanism to explain how STRAP and Smad7 function synergistically to block TGF-beta-induced transcriptional activation. ..
- Zuo W, Huang F, Chiang Y, Li M, Du J, Ding Y, et al. c-Cbl-mediated neddylation antagonizes ubiquitination and degradation of the TGF-? type II receptor. Mol Cell. 2013;49:499-510 pubmed publisher..We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant T?RII neddylation and leukemia development. ..
- Guo W, Dong Z, Guo Y, Chen Z, Yang Z, Kuang G. Association of polymorphisms in transforming growth factor-? receptors with susceptibility to gastric cardia adenocarcinoma. Mol Biol Rep. 2012;39:4301-9 pubmed publisherBoth transforming growth factor-? receptor I (TGFBR1) and receptor II (TGFBR2) are serine/threonine kinases and play important roles in TGF-?/Smads signal pathway...
- Luga V, McLean S, Le Roy C, O Connor McCourt M, Wrana J, Di Guglielmo G. The extracellular domain of the TGFbeta type II receptor regulates membrane raft partitioning. Biochem J. 2009;421:119-31 pubmed publisher..Our results indicate that the extracellular domain of TbetaRII mediates receptor partitioning into membrane rafts and efficient entrance into caveolin-positive endosomes. ..
- Pannu H, Fadulu V, Chang J, Lafont A, Hasham S, Sparks E, et al. Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation. 2005;112:513-20 pubmed..Having mapped a TAAD locus to 3p24-25, we sequenced the gene for transforming growth factor-beta receptor type II (TGFBR2) to determine whether mutations in this gene resulted in familial TAAD...
- Border W, Noble N. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286-92 pubmed
- Guerrero Esteo M, Sanchez Elsner T, Letamendia A, Bernabeu C. Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II. J Biol Chem. 2002;277:29197-209 pubmed..These results suggest that by interacting through its extracellular and cytoplasmic domains with the signaling receptors, endoglin might affect TGF-beta responses. ..
- Borczuk A, Kim H, Yegen H, Friedman R, Powell C. Lung adenocarcinoma global profiling identifies type II transforming growth factor-beta receptor as a repressor of invasiveness. Am J Respir Crit Care Med. 2005;172:729-37 pubmed..The repression of type II TGF-beta receptor may act as a significant determinant of lung adenocarcinoma invasiveness, an early step in tumor progression toward metastasis. ..
- Buck M, Fritz P, Dippon J, Zugmaier G, Knabbe C. Prognostic significance of transforming growth factor beta receptor II in estrogen receptor-negative breast cancer patients. Clin Cancer Res. 2004;10:491-8 pubmed..In addition our results are supportive of a mechanism of breast cancer progression in which a selective loss of the tumor inhibitory action of TGFbeta takes place, whereas tumor- promoting aspects remain intact. ..
- Pezzini A, Drera B, Del Zotto E, Ritelli M, Carletti M, Tomelleri G, et al. Mutations in TGFBR2 gene cause spontaneous cervical artery dissection. J Neurol Neurosurg Psychiatry. 2011;82:1372-4 pubmed publisherMutations in the genes encoding transforming growth factor ? receptors 1 and 2 (TGFBR1 and TGFBR2) have recently been associated with hereditary connective tissue disorders with widespread vascular involvement, including arterial ..
- Bacman D, Merkel S, Croner R, Papadopoulos T, Brueckl W, Dimmler A. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study. BMC Cancer. 2007;7:156 pubmed..Further studies are needed to elucidate the exact mechanisms. ..
- Yu Y, Kanwar S, Patel B, Oh P, Nautiyal J, Sarkar F, et al. MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGF?R2) in colon cancer cells. Carcinogenesis. 2012;33:68-76 pubmed publisher..Our current data suggest that miR-21 plays an important role in regulating stemness by modulating TGF?R2 signaling in colon cancer cells. ..
- Attias D, Stheneur C, Roy C, Collod Beroud G, Detaint D, Faivre L, et al. Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders. Circulation. 2009;120:2541-9 pubmed publisherb>TGFBR2 mutations were recognized recently among patients with a Marfan-like phenotype. The associated clinical and prognostic spectra remain unclear...
- Park S, Lee S, Kim B, Cho E, Patel S, Kang H, et al. Transcriptional regulation of the transforming growth factor beta type II receptor gene by histone acetyltransferase and deacetylase is mediated by NF-Y in human breast cancer cells. J Biol Chem. 2002;277:5168-74 pubmed..Based on these results, we suggest that 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. ..
- Jung B, Smith E, Doctolero R, Gervaz P, Alonso J, Miyai K, et al. Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers. Int J Cancer. 2006;118:2509-13 pubmed..b>TGFBR2 and ACVR2, encoding TGFbeta superfamily receptors, and the proapoptotic gene BAX are frequent targets for ..
- Huang W, Zhao S, Ammanamanchi S, Brattain M, Venkatasubbarao K, Freeman J. Trichostatin A induces transforming growth factor beta type II receptor promoter activity and acetylation of Sp1 by recruitment of PCAF/p300 to a Sp1.NF-Y complex. J Biol Chem. 2005;280:10047-54 pubmed..NF-Y.p300.PCAF.HDAC-1 multiprotein complex. Moreover, the interaction of NF-Y with the Sp1-associated complex may further explain why this specific Sp1 site mediates transcriptional responsiveness to TSA. ..
- Paiva C, Drigo S, Rosa F, Moraes Neto F, Caldeira J, Soares F, et al. Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours. Ann Oncol. 2010;21:734-40 pubmed publisher..These data indicate that TGF-betaRII protein analysis in tumour cells could be introduced in clinical practice as additional prognostic biomarker in HER2-negative BC. ..
- Cheifetz S, Bellon T, Calés C, Vera S, Bernabeu C, Massague J, et al. Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem. 1992;267:19027-30 pubmed..TGF-beta however is binding with high affinity to only a small fraction of the available endoglin molecules, suggesting that some rate-limiting event is required to sustain TGF-beta binding to endoglin. ..
- Noh H, Kim H, Yu M, Kim W, Kim J, Ryu J, et al. Heat shock protein 90 inhibitor attenuates renal fibrosis through degradation of transforming growth factor-? type II receptor. Lab Invest. 2012;92:1583-96 pubmed publisher..These findings suggest that Hsp90 inhibitor prevents the development of renal fibrosis via a mechanism dependent on Smurf2-mediated degradation of T?RII. ..
- Nakao A, Afrakhte M, Moren A, Nakayama T, Christian J, Heuchel R, et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 1997;389:631-5 pubmed..TGF-beta rapidly induces expression of Smad7 mRNA, suggesting that Smad7 may participate in a negative feedback loop to control TGF-beta responses. ..
- Ogasa H, Noma T, Murata H, Kawai S, Nakazawa A. Cloning of a cDNA encoding the human transforming growth factor-beta type II receptor: heterogeneity of the mRNA. Gene. 1996;181:185-90 pubmed..The heterogeneity of TGF-beta IIR molecules could be derived from alternative splicing and might elicit specific TGF-beta receptor functions. ..
- Teixeira L, Lezirovitz K, Mandelbaum K, Pereira L, Perez A. Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome. Braz J Med Biol Res. 2011;44:793-800 pubmed..We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent...
- Huang S, HÃ¶lzel M, Knijnenburg T, Schlicker A, Roepman P, McDermott U, et al. MED12 controls the response to multiple cancer drugs through regulation of TGF-Î² receptor signaling. Cell. 2012;151:937-50 pubmed publisher..Inhibition of TGF-Î²R signaling restores drug responsiveness in MED12(KD) cells, suggesting a strategy to treat drug-resistant tumors that have lost MED12. ..
- Huang L, Liu Z, Lu X, Cui Y. [Expression of transforming growth factor beta receptor I and II in chronic rhinosinusitis, nasal polyps and normal nasal mucosa tissues]. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2006;20:780-3 pubmed..01). The different expression level and pattern of TGFbetaR I and TGFbetaR II in chronic rhinosinusitis and nasal polyps tissues indicates TGFbetaR may play a different role in the pathogenesis chronic rhinosinusitis and nasal polyps. ..
- Lawler S, Feng X, Chen R, Maruoka E, Turck C, Griswold Prenner I, et al. The type II transforming growth factor-beta receptor autophosphorylates not only on serine and threonine but also on tyrosine residues. J Biol Chem. 1997;272:14850-9 pubmed..These results demonstrate that the type II TGF-beta receptor can function as a dual specificity kinase and suggest a role for tyrosine autophosphorylation in TGF-beta receptor signaling. ..
- Lim Y, Jeong Y, Kim S, Kim D, Yun D, Yoo S, et al. Association between TGFBR2 gene polymorphism (rs2228048, Asn389Asn) and intracerebral hemorrhage in Korean population. Immunol Invest. 2011;40:569-80 pubmed publisherTransforming growth factor, beta receptor II (TGFBR2) is mainly expressed by neurons in the central nervous system, and reduced neuronal TGFBR2 signaling results in accelerated age-dependent neurodegeneration...
- Rys J, DuFort C, Monteiro D, Baird M, Oses Prieto J, Chand S, et al. Discrete spatial organization of TGFÎ² receptors couples receptor multimerization and signaling to cellular tension. elife. 2015;4:e09300 pubmed publisher..This work details a novel mechanism by which cellular tension regulates TGFÎ² receptor organization, multimerization, and function, providing new insight into the mechanisms that integrate biochemical and physical cues. ..
- Stolzenburg L, Wachtel S, Dang H, Harris A. miR-1343 attenuates pathways of fibrosis by targeting the TGF-Î² receptors. Biochem J. 2016;473:245-56 pubmed publisher..Mature miR-1343 is readily detected in human neutrophils and HL-60 cells and is activated in response to stress in A549 lung epithelial cells. miR-1343 may have direct therapeutic applications in fibrotic lung disease. ..