Gene Symbol: TGFBR1
Description: transforming growth factor beta receptor 1
Alias: AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1, LDS1A, LDS2A, MSSE, SKR4, TBR-i, TBRI, TGFR-1, tbetaR-I, TGF-beta receptor type-1, activin A receptor type II-like kinase, 53kDa, activin A receptor type II-like protein kinase of 53kD, activin receptor-like kinase 5, mutant transforming growth factor beta receptor I, serine/threonine-protein kinase receptor R4, transforming growth factor beta receptor I, transforming growth factor-beta receptor type I
Species: human
Products:     TGFBR1

Top Publications

  1. 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. ..
  2. Kaklamani V, Baddi L, Rosman D, Liu J, Ellis N, Oddoux C, et al. No major association between TGFBR1*6A and prostate cancer. BMC Genet. 2004;5:28 pubmed
    ..b>TGFBR1*6A, a common hypomorphic variant of the type I Transforming Growth Factor Beta receptor, is emerging as a tumor ..
  3. Chen T, Jackson C, Link A, Markey M, Colligan B, Douglass L, et al. Int7G24A variant of transforming growth factor-beta receptor type I is associated with invasive breast cancer. Clin Cancer Res. 2006;12:392-7 pubmed
    ..An intronic variant (Int7G24A) of TGF-beta receptor type I (TGFBR1) is associated with kidney and bladder cancers in our recent study...
  4. Bian Y, Caldes T, Wijnen J, Franken P, Vasen H, Kaklamani V, et al. TGFBR1*6A may contribute to hereditary colorectal cancer. J Clin Oncol. 2005;23:3074-8 pubmed
    ..121); the difference was not statistically significant (P = .17). TGFBR16A may be causally responsible for a proportion of HNPCC occurrences. ..
  5. Forsti A, Li X, Wagner K, Tavelin B, Enquist K, Palmqvist R, et al. Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression. Genes Chromosomes Cancer. 2010;49:270-81 pubmed publisher
    ..the basis of their reported or predicted functional effect, nine single-nucleotide polymorphisms (TGFB1: Leu10Pro; TGFBR1: 9A/6A and IVS7G+24A; FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G; LTBP4: T-893G and Thr750Ala; BAMBI: T-779A) ..
  6. Colleran G, Mcinerney N, Rowan A, Barclay E, Jones A, Curran C, et al. The TGFBR1*6A/9A polymorphism is not associated with differential risk of breast cancer. Breast Cancer Res Treat. 2010;119:437-42 pubmed publisher
    A polymorphic 9-bp deletion in exon 1 of TGFBR1 (TGFBR1*6A) has been identified as a low-penetrance cancer susceptibility allele...
  7. Hu Y, Pan Y, Li W, Zhang Y, Li J, Ma B. Association between TGFBR1*6A and osteosarcoma: a Chinese case-control study. BMC Cancer. 2010;10:169 pubmed publisher
    b>TGFBR1*6A is a common hypomorphic variant of transforming growth factor beta receptor 1 (TGFBR1). TGFBR1*6A is associated with an increased cancer risk, but the association of this polymorphism with osteosarcoma remains unknown...
  8. 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. ..
  9. Ades L, Sullivan K, Biggin A, Haan E, Brett M, Holman K, et al. FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited. Am J Med Genet A. 2006;140:1047-58 pubmed
    ..2004); Nat Genet 36:855-860] and of TGFBR1 and TGFBR2 mutations in Loeys-Dietz aortic aneurysm syndrome (LDS) [Loeys et al...

More Information


  1. Inman G, Nicolás F, Callahan J, Harling J, Gaster L, Reith A, et al. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol. 2002;62:65-74 pubmed
    ..We demonstrate that it inhibits ALK5 and also the activin type I receptor ALK4 and the nodal type I receptor ALK7, which are very highly related to ALK5 ..
  2. Zhang X, Wu L, Sheng Y, Zhou W, Huang Z, Qu J, et al. The association of polymorphisms on TGFBR1 and colorectal cancer risk: a meta-analysis. Mol Biol Rep. 2012;39:2567-74 pubmed publisher
    Epidemiological studies found inconsistent results on the association of two variants on TGFBR1 (TGFBR1*6A and Int7G24A) with colorectal cancer (CRC) risk...
  3. Groppe J, Hinck C, Samavarchi Tehrani P, Zubieta C, Schuermann J, Taylor A, et al. Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding. Mol Cell. 2008;29:157-68 pubmed publisher
    ..Although structurally similar, BMP and TGF-beta receptors bind in dramatically different modes, mediating graded and switch-like assembly mechanisms that may have coevolved with branch-specific groups of cytoplasmic effectors. ..
  4. Song B, Margolin S, Skoglund J, Zhou X, Rantala J, Picelli S, et al. TGFBR1(*)6A and Int7G24A variants of transforming growth factor-beta receptor 1 in Swedish familial and sporadic breast cancer. Br J Cancer. 2007;97:1175-9 pubmed
    Two common variants in transforming growth factor-beta receptor 1 (TGFBR1), TGFBR1(*)6A and Int7G24A, A allele, have been shown to act as low-penetrance tumour susceptibility alleles in several common cancers, including breast cancer...
  5. Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, et al. Smad6 inhibits signalling by the TGF-beta superfamily. Nature. 1997;389:622-6 pubmed
    ..These data indicate that signals of the TGF-beta superfamily are regulated both positively and negatively by members of the SMAD family. ..
  6. Matyas G, Arnold E, Carrel T, Baumgartner D, Boileau C, Berger W, et al. Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders. Hum Mutat. 2006;27:760-9 pubmed
    Very recently, heterozygous mutations in the genes encoding transforming growth factor beta receptors I (TGFBR1) and II (TGFBR2) have been reported in Loeys-Dietz aortic aneurysm syndrome (LDS)...
  7. Thomas M, Docx C, Holmes A, Beach S, Duggan N, England K, et al. Activin-like kinase 5 (ALK5) mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by mon. Am J Pathol. 2009;174:380-9 pubmed publisher
    ..Collectively, these data are consistent with a role for the activin receptor-like kinase 5 in the progression of idiopathic PAH and imply that strategies to inhibit activin receptor-like kinase 5 signaling may have therapeutic benefit. ..
  8. 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. ..
  9. Massague J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753-91 pubmed
    ..Mutations in these pathways are the cause of various forms of human cancer and developmental disorders. ..
  10. Seguí N, Stevens K, Guino E, Rozek L, Moreno V, Capella G, et al. No association between germline allele-specific expression of TGFBR1 and colorectal cancer risk in Caucasian and Ashkenazi populations. Br J Cancer. 2011;104:735-40 pubmed publisher
    Germline allele-specific expression (ASE) of the TGFBR1 gene has been reported as a strong risk factor for colorectal cancer (CRC) with an odds ratio close to 9...
  11. Zhang H. Int7G24A variant of the TGFBR1 gene and cancer risk: a meta-analysis of three case-control studies. Lung Cancer. 2005;49:419-20 pubmed
  12. Castillejo A, Mata Balaguer T, Guarinos C, Castillejo M, Martinez Canto A, Barbera V, et al. The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study. BMC Cancer. 2009;9:406 pubmed publisher
    The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1) has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC) has not been established...
  13. Zhang Y, Liu B, Jin M, Ni Q, Liang X, Ma X, et al. Genetic polymorphisms of transforming growth factor-beta1 and its receptors and colorectal cancer susceptibility: a population-based case-control study in China. Cancer Lett. 2009;275:102-8 pubmed publisher
    ..05-1.66). Our findings indicate that the distributions of polymorphisms in TGF-beta1 and its receptors genes vary greatly among different ethnic groups, and these polymorphisms might contribute to the colorectal cancer susceptibility. ..
  14. Ozdamar B, Bose R, Barrios Rodiles M, Wang H, Zhang Y, Wrana J. Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science. 2005;307:1603-9 pubmed
    ..These studies define how an extracellular cue signals to the polarity machinery to control epithelial cell morphology. ..
  15. Skoglund J, Song B, Dalén J, Dedorson S, Edler D, Hjern F, et al. Lack of an association between the TGFBR1*6A variant and colorectal cancer risk. Clin Cancer Res. 2007;13:3748-52 pubmed
    Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are ..
  16. Eichhorn P, Rodón L, Gonzàlez Juncà A, Dirac A, Gili M, Martínez Sáez E, et al. USP15 stabilizes TGF-? receptor I and promotes oncogenesis through the activation of TGF-? signaling in glioblastoma. Nat Med. 2012;18:429-35 pubmed publisher
    ..Our results show that USP15 regulates the TGF-? pathway and is a key factor in glioblastoma pathogenesis. ..
  17. Jachec W, Foremny A, Domal Kwiatkowska D, Smolik S, Tomasik A, Mazurek U, et al. Expression of TGF-beta1 and its receptor genes (TbetaR I, TbetaR II, and TbetaR III-betaglycan) in peripheral blood leucocytes in patients with idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome. Int J Mol Med. 2008;21:99-107 pubmed
    ..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 [..
  18. Martinez Canto A, Castillejo A, Mata Balaguer T, Castillejo M, Hernandez Illan E, Irles E, et al. TGFBR1 intralocus epistatic interaction as a risk factor for colorectal cancer. PLoS ONE. 2012;7:e30812 pubmed publisher
    ..We assessed the susceptibility to CRC conferred by genetic variants at the TGFBR1 locus...
  19. Tsukazaki T, Chiang T, Davison A, Attisano L, Wrana J. SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. Cell. 1998;95:779-91 pubmed
    ..These results thus define SARA as a component of the TGFbeta pathway that brings the Smad substrate to the receptor. ..
  20. Saitoh M, Nishitoh H, Amagasa T, Miyazono K, Takagi M, Ichijo H. Identification of important regions in the cytoplasmic juxtamembrane domain of type I receptor that separate signaling pathways of transforming growth factor-beta. J Biol Chem. 1996;271:2769-75 pubmed
    ..These observations indicate that serine 172 and threonine 176 of T beta R-I are dispensable for extracellular matrix protein production but essential to the growth inhibition by TGF-beta. ..
  21. Liao R, Mao C, Qiu L, Ding H, Chen Q, Pan H. TGFBR1*6A/9A polymorphism and cancer risk: a meta-analysis of 13,662 cases and 14,147 controls. Mol Biol Rep. 2010;37:3227-32 pubmed publisher
    Published data on the association between TGFBR1*6A/9A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed...
  22. Guda K, Natale L, Lutterbaugh J, Wiesner G, Lewis S, Tanner S, et al. Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients. Cancer Res. 2009;69:4959-61 pubmed publisher
    ..allele-specific expression (ASE) of the gene encoding for transforming growth factor-beta type I receptor (TGFBR1) has been proposed to be a major risk factor for cancer predisposition in the colon...
  23. Suarez B, Pal P, Jin C, Kaushal R, Sun G, Jin L, et al. TGFBR1*6A is not associated with prostate cancer in men of European ancestry. Prostate Cancer Prostatic Dis. 2005;8:50-3 pubmed
    The TGFBR1*6A (*6A) variant in exon 1 of the TGFBR1 gene has been postulated as a putative tumor susceptibility allele in several studies...
  24. Rotzer D, Roth M, Lutz M, Lindemann D, Sebald W, Knaus P. Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor. EMBO J. 2001;20:480-90 pubmed
    ..The expression of TbetaRII-B is restricted to cells originating from tissues such as bone where the isoform TGF-beta2 has a predominant role. This reflects the importance of this receptor in TGF-beta isoform-specific signalling. ..
  25. Johnson D, Qumsiyeh M, Benkhalifa M, Marchuk D. Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively. Genomics. 1995;28:356-7 pubmed
  26. 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. ..
  27. Wicks S, Haros K, Maillard M, Song L, Cohen R, Dijke P, et al. The deubiquitinating enzyme UCH37 interacts with Smads and regulates TGF-beta signalling. Oncogene. 2005;24:8080-4 pubmed
    ..These findings support a new role for deubiquitinating enzymes in the control of the TGF-beta signalling pathway, and provide a novel molecular target for the design of inhibitors with therapeutic potential in cancer. ..
  28. Loeys B, Schwarze U, Holm T, Callewaert B, Thomas G, Pannu H, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006;355:788-98 pubmed
    ..and is caused by heterozygous mutations in the genes encoding transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2, respectively). We undertook the clinical and molecular characterization of 52 affected families...
  29. Yamashita M, Fatyol K, Jin C, Wang X, Liu Z, Zhang Y. TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta. Mol Cell. 2008;31:918-24 pubmed publisher
    ..Our results indicate that TGF-beta activates JNK and p38 through a mechanism similar to that operating in the interleukin-1beta/Toll-like receptor pathway. ..
  30. Liu C, Xu P, Lamouille S, Xu J, Derynck R. TACE-mediated ectodomain shedding of the type I TGF-beta receptor downregulates TGF-beta signaling. Mol Cell. 2009;35:26-36 pubmed publisher
    ..The decreased growth inhibition by TGF-beta, due to elevated TACE activity, complements the growth stimulation resulting from increased release of TGF-alpha family ligands. ..
  31. Castillejo A, Rothman N, Murta Nascimento C, Malats N, Garcia Closas M, Gómez Martínez A, et al. TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis. Int J Cancer. 2009;124:608-13 pubmed publisher
    ..7 different common variants in genes coding for 2 key members of the TGF-beta signalling pathway (TGFB1 and TGFBR1) are associated with bladder cancer risk and prognosis...
  32. 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...
  33. Valle L, Serena Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, et al. Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science. 2008;321:1361-5 pubmed publisher
    ..allele-specific expression (ASE) of the gene encoding transforming growth factor-beta (TGF-beta) type I receptor, TGFBR1, is a quantitative trait that occurs in 10 to 20% of CRC patients and 1 to 3% of controls...
  34. Wang Y, Qi X, Wang F, Jiang J, Guo Q. Association between TGFBR1 polymorphisms and cancer risk: a meta-analysis of 35 case-control studies. PLoS ONE. 2012;7:e42899 pubmed publisher
    Numerous epidemiological studies have evaluated the association between TGFBR1 polymorphisms and the risk of cancer, however, the results remain inconclusive...
  35. Loeys B, Chen J, Neptune E, Judge D, Podowski M, Holm T, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005;37:275-81 pubmed
  36. Wang T, Donahoe P, Zervos A. Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12. Science. 1994;265:674-6 pubmed
    ..The specific interaction between the type I receptors and FKBP-12 suggests that FKBP-12 may play a role in type I receptor-mediated signaling. ..
  37. Spillman M, Schildkraut J, Halabi S, Moorman P, Calingaert B, Bentley R, et al. Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk. Gynecol Oncol. 2005;97:543-9 pubmed
    ..Larger studies would be needed to exclude the possibility that the small fraction of individuals who are 6A homozygotes have an increased risk of ovarian or other cancers. ..
  38. Wrighton K, Lin X, Feng X. Critical regulation of TGFbeta signaling by Hsp90. Proc Natl Acad Sci U S A. 2008;105:9244-9 pubmed publisher
    ..Our data reveal an essential level of TGFbeta signaling regulation mediated by Hsp90 by its ability to chaperone TbetaRs and also implicate the use of Hsp90 inhibitors in blocking undesired activation of TGFbeta signaling in diseases. ..
  39. 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 pubmed
    In 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...
  40. Kaklamani V, Hou N, Bian Y, Reich J, Offit K, Michel L, et al. TGFBR1*6A and cancer risk: a meta-analysis of seven case-control studies. J Clin Oncol. 2003;21:3236-43 pubmed
    b>TGFBR1*6A is a hypomorphic polymorphic allele of the type I transforming growth factor beta receptor (TGFBR1)...
  41. Baxter S, Choong D, Eccles D, Campbell I. Transforming growth factor beta receptor 1 polyalanine polymorphism and exon 5 mutation analysis in breast and ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2002;11:211-4 pubmed
  42. Cox D, Penney K, Guo Q, Hankinson S, Hunter D. TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses' Health Study. BMC Cancer. 2007;7:175 pubmed
    ..Single nucleotide polymorphisms in TGFB1 and a microsatellite in TGFBR1 have been investigated for association with risk of breast cancer, with conflicting results...
  43. Chen T, Jackson C, Costello B, Singer N, Colligan B, Douglass L, et al. An intronic variant of the TGFBR1 gene is associated with carcinomas of the kidney and bladder. Int J Cancer. 2004;112:420-5 pubmed
    ..Genetic alterations of the TGF-beta type 1 receptor (TGFBR1) may contribute to these perturbations...
  44. Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, et al. Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 2003;22:6458-70 pubmed
    ..Arkadia may thus play an important role as an amplifier of TGF-beta superfamily signalling under both physiological and pathological conditions. ..
  45. Bian Y, Knobloch T, Sadim M, Kaklamani V, Raji A, Yang G, et al. Somatic acquisition of TGFBR1*6A by epithelial and stromal cells during head and neck and colon cancer development. Hum Mol Genet. 2007;16:3128-35 pubmed
    b>TGFBR1*6A is a common hypomorphic variant of the type I transforming growth factor (TGF)-beta receptor (TGFBR1), which transduces TGF-beta growth inhibitory signals less effectively than TGFBR1...
  46. Franzen P, ten Dijke P, Ichijo H, Yamashita H, Schulz P, Heldin C, et al. Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptor. Cell. 1993;75:681-92 pubmed
    ..These results suggest that signal transduction by TGF beta involves the formation of a heteromeric complex of two different serine/threonine kinase receptors. ..
  47. Macias Silva M, Abdollah S, Hoodless P, Pirone R, Attisano L, Wrana J. MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell. 1996;87:1215-24 pubmed
    ..Thus, transient association and phosphorylation of MADR2 by the TGFbeta receptor is necessary for nuclear accumulation and initiation of signaling. ..
  48. Samowitz W, Curtin K, Leppert M, Slattery M. Uncommon TGFBRI allele is not associated with increased susceptibility to colon cancer. Genes Chromosomes Cancer. 2001;32:381-3 pubmed
    ..We conclude that the 6A TGFBRI allele is not associated with an increased susceptibility to colon cancer at the population level, and that the 6A/6A homozygote is not restricted to individuals with some form of cancer. ..
  49. Pasche B, Luo Y, Rao P, Nimer S, Dmitrovsky E, Caron P, et al. Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract. Cancer Res. 1998;58:2727-32 pubmed
    ..The clinical and biological significance of TbetaR-I(6A) homozygosity needs to be further investigated. ..
  50. Lin H, Moustakas A, Knaus P, Wells R, Henis Y, Lodish H. The soluble exoplasmic domain of the type II transforming growth factor (TGF)-beta receptor. A heterogeneously glycosylated protein with high affinity and selectivity for TGF-beta ligands. J Biol Chem. 1995;270:2747-54 pubmed
    ..Thus, the type III receptor or some other component is required for transmission of TGF-beta 2-induced signals by the type II receptor. ..
  51. Wilkes M, Murphy S, Garamszegi N, Leof E. Cell-type-specific activation of PAK2 by transforming growth factor beta independent of Smad2 and Smad3. Mol Cell Biol. 2003;23:8878-89 pubmed
    ..Thus, PAK2 represents a novel Smad-independent pathway that differentiates TGF-beta signaling in fibroblast (growth-stimulated) and epithelial cell (growth-inhibited) cultures. ..
  52. Attisano L, Carcamo J, Ventura F, Weis F, Massague J, Wrana J. Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors. Cell. 1993;75:671-80 pubmed
    ..The results indicate that type I receptors are transmembrane protein kinases that associate with type II receptors to generate diverse heteromeric serine/threonine kinase complexes of different signaling capacities. ..
  53. 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. ..
  54. Vellucci V, Reiss M. Cloning and genomic organization of the human transforming growth factor-beta type I receptor gene. Genomics. 1997;46:278-83 pubmed
    ..We determined the intron-exon organization of the TGFBR1 gene. We report here that this gene is approximately 31 kb in length and consists of nine exons...
  55. 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. ..
  56. Kaklamani V, Baddi L, Liu J, Rosman D, Phukan S, Bradley C, et al. Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. Cancer Res. 2005;65:3454-61 pubmed
    ..Cancer Center (New York, NY) and healthy females (n = 880) from New York City were genotyped for the hypomorphic TGFBR1*6A allele and for the TGFB1 T29C variant that results in increased TGF-beta circulating levels...
  57. 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. ..
  58. Abdollah S, Macias Silva M, Tsukazaki T, Hayashi H, Attisano L, Wrana J. TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling. J Biol Chem. 1997;272:27678-85 pubmed
    ..These results indicate that receptor-dependent phosphorylation of Smad2 on serines 465 and 467 is required in mammalian cells to permit association with Smad4 and to propagate TGF-beta signals. ..
  59. Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, et al. The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol. 2008;10:1199-207 pubmed publisher
    ..Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6. ..
  60. Seong H, Jung H, Ha H. NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and negatively regulates TGF-beta signaling. J Biol Chem. 2007;282:12075-96 pubmed
    ..These results suggest that the direct interaction of NM23-H1 and STRAP is important for the regulation of TGF-beta-dependent biological activity as well as NM23-H1 activity. ..
  61. Daley D, Morgan W, Lewis S, Willis J, Elston R, Markowitz S, et al. Is TGFBR1*6A a susceptibility allele for nonsyndromic familial colorectal neoplasia?. Cancer Epidemiol Biomarkers Prev. 2007;16:892-4 pubmed
    Our analysis definitely excludes the possibility of the TGFBR1*6A allele increasing the risk of colorectal neoplasia in our sample population...
  62. Rosman D, Phukan S, Huang C, Pasche B. TGFBR1*6A enhances the migration and invasion of MCF-7 breast cancer cells through RhoA activation. Cancer Res. 2008;68:1319-28 pubmed publisher
    b>TGFBR1*6A is a common hypomorphic variant of the type 1 transforming growth factor beta receptor (TGFBR1), which has been associated with increased cancer risk in some studies...
  63. Souchelnytskyi S, Nakayama T, Nakao A, Moren A, Heldin C, Christian J, et al. Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. J Biol Chem. 1998;273:25364-70 pubmed
    ..Our results are consistent with the possibility that the C-domain of antagonistic Smads is an effector domain whereas the N-domain may confer specificity for distinct signaling pathways. ..
  64. Massague J. Receptors for the TGF-beta family. Cell. 1992;69:1067-70 pubmed
  65. Ammanamanchi S, Brattain M. Restoration of transforming growth factor-beta signaling through receptor RI induction by histone deacetylase activity inhibition in breast cancer cells. J Biol Chem. 2004;279:32620-5 pubmed
    ..Significantly, SAHA-mediated RI regeneration restored the TGF-beta response in breast cancer cells. ..
  66. Hayashi H, Abdollah S, Qiu Y, Cai J, Xu Y, Grinnell B, et al. The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell. 1997;89:1165-73 pubmed
    ..These studies thus define a novel function for MAD-related proteins as intracellular antagonists of the type I kinase domain of TGFbeta family receptors. ..
  67. 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 publisher
    Both transforming growth factor-? receptor I (TGFBR1) and receptor II (TGFBR2) are serine/threonine kinases and play important roles in TGF-?/Smads signal pathway...
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    b>TGFBR1*6A, a functionally polymorphic allele in the transforming growth factor [beta] receptor 1 gene (TGFBR1), has been hypothesized to increase risk of various cancers...
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    ..However, for B-lineage ALL, the role of the rs10417924 polymorphism in TGF-beta1 gene needs further investigation. ..
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    TGF-beta receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-beta receptor I gene and has been associated with tumour susceptibility...
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    The role of transforming growth factor beta receptor type 1 (TGFBR1) polymorphisms, particularly a coding CGC insertion (rs11466445, TGFBR1*6A/9A) in exon 1, has been extensively investigated in regard to colorectal cancer (CRC) risk...
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    ..It is concluded that Int7G24A is a polymorphism of TGFBR1 that is associated with the susceptibility and distant metastasis of osteosarcoma.
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    ..Treatment with TGF-beta or expression of an activated TGF-beta type I receptor (Alk5 with the mutation T204D [Alk5(T204D)]) induced phosphorylation of TACE/ADAM17 and its translocation to the cell ..
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    ..We recently suggested that a subtle decrease in the expression of one allele of the TGFBR1 gene was a heritable quantitative trait predisposing to CRC...
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    ..These results define hMAD-3 and -4 as effectors of the TGF-beta response and demonstrate a function for DPCA-4/hMAD-4 as a tumour suppressor. ..
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    Variants of the transforming growth factor-beta receptor type 1 (TGFBR1) gene, TGFBR1*6A and Int7G24A, have been suggested to act as low-penetrance tumour susceptibility alleles with TGFBR1*6A being causally responsible for some cases of ..
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    ..These results suggest that by interacting through its extracellular and cytoplasmic domains with the signaling receptors, endoglin might affect TGF-beta responses. ..
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    ..Thus, we describe a mechanism to explain how STRAP and Smad7 function synergistically to block TGF-beta-induced transcriptional activation. ..