Gene Symbol: Tgfbr1
Description: transforming growth factor, beta receptor I
Alias: ALK5, AU017191, Alk-5, ESK2, TGFR-1, TbetaR-I, TbetaRI, TGF-beta receptor type-1, TGF-beta receptor type I, transforming growth factor-beta receptor type I
Species: mouse
Products:     Tgfbr1

Top Publications

  1. Honjo Y, Bian Y, Kawakami K, Molinolo A, Longenecker G, Boppana R, et al. TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma. Cell Cycle. 2007;6:1360-6 pubmed
    ..a mouse model with a conditional deletion of TGF-beta signaling in the neurons by crossing TGF-beta receptor I (TbetaRI) floxed mice with neurofilament-H (NF-H) Cre mice...
  2. Park S, Lee Y, Seki T, Hong K, Fliess N, Jiang Z, et al. ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2. Blood. 2008;111:633-42 pubmed
    ..In cultured endothelial cells, ALK1 and another TGF-beta type I receptor, ALK5, regulate angiogenesis by controlling TGF-beta signal transduction, and ALK5 is required for ALK1 signaling...
  3. Liu Y, Zhang P, Li J, Kulkarni A, Perruche S, Chen W. A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells. Nat Immunol. 2008;9:632-40 pubmed publisher
    ..We show here that conditional deletion of transforming growth factor-beta receptor I (TbetaRI) in T cells blocked the appearance of CD4+CD25+Foxp3+ thymocytes at postnatal days 3-5...
  4. Matsunobu T, Torigoe K, Ishikawa M, de Vega S, Kulkarni A, Iwamoto Y, et al. Critical roles of the TGF-beta type I receptor ALK5 in perichondrial formation and function, cartilage integrity, and osteoblast differentiation during growth plate development. Dev Biol. 2009;332:325-38 pubmed publisher
    ..signaling in growth plate development by creating mice with a conditional knockout of the TGF-beta type I receptor ALK5 (ALK5(CKO)) in skeletal progenitor cells using Dermo1-Cre mice...
  5. Ray B, Lee N, How T, Blobe G. ALK5 phosphorylation of the endoglin cytoplasmic domain regulates Smad1/5/8 signaling and endothelial cell migration. Carcinogenesis. 2010;31:435-41 pubmed publisher
    ..cells through regulating the balance between two TGF-beta-responsive pathways, the activin receptor-like kinase 5 (ALK5)/Smad2/3 pathway and the activin receptor-like kinase 1 (ALK1)/Smad1/5/8 pathway, the mechanism by which endoglin ..
  6. Xiao X, Wiersch J, El Gohary Y, Guo P, Prasadan K, Paredes J, et al. TGF? receptor signaling is essential for inflammation-induced but not ?-cell workload-induced ?-cell proliferation. Diabetes. 2013;62:1217-26 pubmed publisher
    ..Our study thus provides important information for understanding ?-cell proliferation during normal growth and in pancreatic diseases. ..
  7. Taya Y, O Kane S, Ferguson M. Pathogenesis of cleft palate in TGF-beta3 knockout mice. Development. 1999;126:3869-79 pubmed
  8. Zhang L, Zhou F, Drabsch Y, Gao R, Snaar Jagalska B, Mickanin C, et al. USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-? type I receptor. Nat Cell Biol. 2012;14:717-26 pubmed publisher
    ..Moreover, AKT-induced breast cancer cell migration was inhibited by USP4 depletion and T?RI kinase inhibition. Our results uncover USP4 as an important determinant for crosstalk between TGF-? and AKT signalling pathways. ..
  9. Tulachan S, Tei E, Hembree M, Crisera C, Prasadan K, Koizumi M, et al. TGF-beta isoform signaling regulates secondary transition and mesenchymal-induced endocrine development in the embryonic mouse pancreas. Dev Biol. 2007;305:508-21 pubmed
    ..TGF-beta RII in the ducts and islets may normally serve to downregulate the production of beta cells from embryonic ducts. ..

More Information


  1. Li M, Li C, Liu Y, Xing Y, Hu L, Borok Z, et al. Mesodermal deletion of transforming growth factor-beta receptor II disrupts lung epithelial morphogenesis: cross-talk between TGF-beta and Sonic hedgehog pathways. J Biol Chem. 2008;283:36257-64 pubmed publisher
    ..To our knowledge, this is the first in vivo evidence for a reciprocal and novel mode of cross-communication between Shh and TGF-beta pathways during embryonic development. ..
  2. Liu I, Schilling S, Knouse K, Choy L, Derynck R, Wang X. TGFbeta-stimulated Smad1/5 phosphorylation requires the ALK5 L45 loop and mediates the pro-migratory TGFbeta switch. EMBO J. 2009;28:88-98 pubmed publisher
    ..event requires the kinase activity and, unexpectedly, the L45 loop motif of the type I TGFbeta receptor, ALK5, as evidenced by studies using short hairpin RNA-resistant ALK5 mutants in ALK5-depleted cells and in vitro kinase ..
  3. Moreno S, Attali M, Allemand I, Messiaen S, Fouchet P, Coffigny H, et al. TGFbeta signaling in male germ cells regulates gonocyte quiescence and fertility in mice. Dev Biol. 2010;342:74-84 pubmed publisher
  4. Xing Y, Li C, Li A, Sridurongrit S, Tiozzo C, Bellusci S, et al. Signaling via Alk5 controls the ontogeny of lung Clara cells. Development. 2010;137:825-33 pubmed publisher
    ..In this study, we deleted the TGFbeta type I receptor Alk5 in the embryonic lung epithelium using Gata5-Cre mice...
  5. Egorova A, Van der Heiden K, van de Pas S, Vennemann P, Poelma C, DeRuiter M, et al. Tgf?/Alk5 signaling is required for shear stress induced klf2 expression in embryonic endothelial cells. Dev Dyn. 2011;240:1670-80 pubmed publisher
    ..Results show that, in embryonic EC, shear stress activates Tgf?/Alk5 signaling and that induction of Klf2 is an Alk5 dependent process.
  6. Sun Z, Zhang L, Hall B, Bian Y, Gutkind J, Kulkarni A. Chemopreventive and chemotherapeutic actions of mTOR inhibitor in genetically defined head and neck squamous cell carcinoma mouse model. Clin Cancer Res. 2012;18:5304-13 pubmed publisher
    ..Knockdown of Tgfbr1 and/or Pten using siRNA-mediated RNA interference was carried out in human HNSCC cell lines to analyze molecular ..
  7. Alejandre Alcazar M, Michiels Corsten M, Vicencio A, Reiss I, Ryu J, de Krijger R, et al. TGF-beta signaling is dynamically regulated during the alveolarization of rodent and human lungs. Dev Dyn. 2008;237:259-69 pubmed
    ..Pronounced changes in the expression and localization of the TGF-beta receptors Acvrl1, Tgfbr1, Tgfbr2, Tgfbr3, and endoglin, and the intracellular messengers Smad2, Smad3, Smad4, Smad6, and Smad7 were noted ..
  8. Roelen B, Lin H, Knezevic V, Freund E, Mummery C. Expression of TGF-beta s and their receptors during implantation and organogenesis of the mouse embryo. Dev Biol. 1994;166:716-28 pubmed
  9. Wu H, Ivkovic S, Murray R, Jaramillo S, Lyons K, Johnson J, et al. Autoregulation of neurogenesis by GDF11. Neuron. 2003;37:197-207 pubmed
  10. Perruche S, Zhang P, Maruyama T, Bluestone J, Saas P, Chen W. Lethal effect of CD3-specific antibody in mice deficient in TGF-beta1 by uncontrolled flu-like syndrome. J Immunol. 2009;183:953-61 pubmed publisher
    ..The study may also provide a novel molecular mechanism explaining the early death in TGF-beta1(-/-) mice. ..
  11. Goumans M, Valdimarsdottir G, Itoh S, Lebrin F, Larsson J, Mummery C, et al. Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFbeta/ALK5 signaling. Mol Cell. 2003;12:817-28 pubmed
    ..induces Smad1/5 phosphorylation, leading to an increase in endothelial cell proliferation and migration, while ALK5 promotes Smad2/3 activation and inhibits both processes...
  12. Zhang L, Sun Z, Bian Y, Kulkarni A. MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma. Cancer Lett. 2013;331:230-8 pubmed publisher
    ..Thus, our data demonstrate that miR-135b acts as a tumor promoter by promoting cancer cell proliferation, colony formation, survival, and angiogenesis through activation of HIF-1α in HNSCC. ..
  13. Bian Y, Terse A, Du J, Hall B, Molinolo A, Zhang P, et al. Progressive tumor formation in mice with conditional deletion of TGF-beta signaling in head and neck epithelia is associated with activation of the PI3K/Akt pathway. Cancer Res. 2009;69:5918-26 pubmed publisher
    ..we report generation of an inducible head- and neck-specific knockout mouse model by crossing TGF-beta receptor I (Tgfbr1) floxed mice with K14-CreER(tam) mice...
  14. Hao X, Wang Y, Ren F, Zhu S, Ren Y, Jia B, et al. SNX25 regulates TGF-? signaling by enhancing the receptor degradation. Cell Signal. 2011;23:935-46 pubmed publisher
    ..We have characterized that PXA domain of SNX25 is required for the degradation of T?RI. Our findings demonstrate that SNX25 negatively regulates TGF-? signaling by enhancing the receptor degradation through lysosome pathway. ..
  15. Yi J, Barnes A, Hand R, Polleux F, Ehlers M. TGF-beta signaling specifies axons during brain development. Cell. 2010;142:144-57 pubmed publisher
    ..These results define an extrinsic cue for neuronal polarity in vivo that patterns neural circuits in the developing brain. ..
  16. Larsson J, Goumans M, Sjöstrand L, Van Rooijen M, Ward D, Leveen P, et al. Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice. EMBO J. 2001;20:1663-73 pubmed
    ..To define the function of TGF-beta more precisely, we inactivated the TGF-beta type I receptor (TbetaRI) gene by gene targeting...
  17. Wang J, Nagy A, Larsson J, Dudas M, Sucov H, Kaartinen V. Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects. BMC Dev Biol. 2006;6:51 pubmed
    ..We deleted the TGF-beta type I receptor Alk5 specifically in the mouse neural crest cell lineage...
  18. Dudas M, Kim J, Li W, Nagy A, Larsson J, Karlsson S, et al. Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion. Dev Biol. 2006;296:298-314 pubmed
    ..Here, we deleted the TGF-beta type I receptor gene Alk5 specifically in the embryonic ectodermal and neural crest cell lineages...
  19. Tesseur I, Wyss Coray T. A role for TGF-beta signaling in neurodegeneration: evidence from genetically engineered models. Curr Alzheimer Res. 2006;3:505-13 pubmed
    ..Future studies will have to determine whether dysregulation of TGF-beta signaling in neurodegenerative diseases is significant and whether this signaling pathway may even be a target for treatment. ..
  20. Carvalho R, Itoh F, Goumans M, Lebrin F, Kato M, Takahashi S, et al. Compensatory signalling induced in the yolk sac vasculature by deletion of TGFbeta receptors in mice. J Cell Sci. 2007;120:4269-77 pubmed
    ..To address this, we selectively deleted the type I (ALK5, TGFBR1) and type II (TbetaRII, TGFBR2) receptors in mice...
  21. Upadhyay G, Yin Y, Yuan H, Li X, Derynck R, Glazer R. Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)-dependent TGF-beta signaling. Proc Natl Acad Sci U S A. 2011;108:7820-5 pubmed publisher
    ..These findings suggest a new functional role for Sca-1 in maintaining tumorigenicity, in part by acting as a potent suppressor of TGF-? signaling. ..
  22. Bian Y, Hall B, Sun Z, Molinolo A, Chen W, Gutkind J, et al. Loss of TGF-β signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation. Oncogene. 2012;31:3322-32 pubmed publisher
    ..However, Pten-deficient mice developed full-penetrance HNSCC in combination with type I TGF-β receptor (Tgfbr1) deletion...
  23. Lai Y, Beason K, Brames G, Desgrosellier J, Cleggett M, Shaw M, et al. Activin receptor-like kinase 2 can mediate atrioventricular cushion transformation. Dev Biol. 2000;222:1-11 pubmed
    ..we cloned and characterized the chicken homologues of two mammalian activin receptor-like kinases (ALK), ALK2 and ALK5, and generated specific, polyclonal antibodies against the extracellular binding domains of each...
  24. Principe D, DeCant B, Mascariñas E, Wayne E, Diaz A, Akagi N, et al. TGFβ Signaling in the Pancreatic Tumor Microenvironment Promotes Fibrosis and Immune Evasion to Facilitate Tumorigenesis. Cancer Res. 2016;76:2525-39 pubmed publisher
    ..Cancer Res; 76(9); 2525-39. ©2016 AACR. ..
  25. Nguyen H, Lee Y, Shin J, Lee E, Park S, McCarty J, et al. TGF-? signaling in endothelial cells, but not neuroepithelial cells, is essential for cerebral vascular development. Lab Invest. 2011;91:1554-63 pubmed publisher
    ..In contrast, selective deletion of the Tgfbr2 or Alk5 genes in ECs result in embryonic lethality because of brain-specific vascular pathologies, including blood vessel ..
  26. Zahner S, Kel J, Martina C, Brouwers Haspels I, van Roon M, Clausen B. Conditional deletion of TGF-?R1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity. J Immunol. 2011;187:5069-76 pubmed publisher
    ..Moreover, these Langerin-Cre mice represent a unique and powerful tool to dissect the role and molecular control of Langerin(+) DC populations beyond LC. ..
  27. Gründer A, Ebel T, Mallo M, Schwarzkopf G, Shimizu T, Sippel A, et al. Nuclear factor I-B (Nfib) deficient mice have severe lung hypoplasia. Mech Dev. 2002;112:69-77 pubmed
    ..Our study demonstrates that Nfib is essential for normal lung development, and suggests that it could be involved in the pathogenesis of respiratory distress syndromes in humans. ..
  28. Kolodziejczyk S, Hall B. Signal transduction and TGF-beta superfamily receptors. Biochem Cell Biol. 1996;74:299-314 pubmed
    ..The myriad responses regulated by TGF-beta superfamily members makes the understanding of signal transduction mechanisms utilized by these proteins of great interest to a wide range of biological disciplines. ..
  29. Wang X, Abraham S, McKenzie J, Jeffs N, Swire M, Tripathi V, et al. LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling. Nature. 2013;499:306-11 pubmed publisher
    ..LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a new regulator of angiogenesis that mediates its effect by modulating TGF-β signalling. ..
  30. Wang Y, Du J, Niu X, Fu N, Wang R, Zhang Y, et al. MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2. Cell Death Dis. 2017;8:e2792 pubmed publisher
    ..The hepatic expression of TGFBR1 and TGFBR2 was significantly increased...
  31. Liao M, Zhou J, Wang F, Ali Y, Chan K, Zou F, et al. An X-linked Myh11-CreERT2 mouse line resulting from Y to X chromosome-translocation of the Cre allele. Genesis. 2017;55: pubmed publisher
    ..In a model of aortic aneurysm induced by a SMC-specific Tgfbr1 deletion, the homozygous XCre+ /XCre+ Cre driver unmasked the aortic phenotype that is ..
  32. Kondo T, Ishiga Hashimoto N, Nagai H, Takeshita A, Mino M, Morioka H, et al. Expression of transforming growth factor ? and fibroblast growth factor 2 in the lens epithelium of Morioka cataract mice. Congenit Anom (Kyoto). 2014;54:104-9 pubmed publisher
  33. Iseki S, Osumi Yamashita N, Miyazono K, Franzen P, Ichijo H, Ohtani H, et al. Localization of transforming growth factor-beta type I and type II receptors in mouse development. Exp Cell Res. 1995;219:339-47 pubmed
  34. Wang W, Zhao Z, Ma S, Yu G, Liu B, Zhang L, et al. Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and Notch1 in head neck squamous cell carcinoma. PLoS ONE. 2015;10:e0119723 pubmed publisher
    ..EGFR was overexpressed and activated in the Tgfbr1/Pten deletion (2cKO) mouse model of HNSCC...
  35. James J, Nalbandian A, Mukouyama Y. TGF? signaling is required for sprouting lymphangiogenesis during lymphatic network development in the skin. Development. 2013;140:3903-14 pubmed publisher
    ..We utilized a series of conditional mutants to ablate the TGF? receptors Tgfbr1 (Alk5) and Tgfbr2 in LECs...
  36. Al Salihi M, Herhaus L, MacArtney T, Sapkota G. USP11 augments TGF? signalling by deubiquitylating ALK5. Open Biol. 2012;2:120063 pubmed publisher
    ..USP11 interacts with and deubiquitylates the type I TGF? receptor (ALK5), resulting in enhanced TGF?-induced gene transcription...
  37. Peters D, Vadász I, Wujak L, Wygrecka M, Olschewski A, Becker C, et al. TGF-? directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury. Proc Natl Acad Sci U S A. 2014;111:E374-83 pubmed publisher
    ..fluids from ARDS patients drove ?ENaC internalization, which was inhibited by a TGF-? neutralizing antibody and a Tgfbr1 inhibitor...
  38. Gallo E, Loch D, Habashi J, Calderon J, Chen Y, Bedja D, et al. Angiotensin II-dependent TGF-? signaling contributes to Loeys-Dietz syndrome vascular pathogenesis. J Clin Invest. 2014;124:448-60 pubmed publisher
    ..LDS is caused by heterozygous missense mutations in either TGF-? receptor gene (TGFBR1 or TGFBR2), which are predicted to result in diminished TGF-? signaling; however, aortic surgical samples from ..
  39. Nik A, Johansson J, Ghiami M, Reyahi A, Carlsson P. Foxf2 is required for secondary palate development and Tgf? signaling in palatal shelf mesenchyme. Dev Biol. 2016;415:14-23 pubmed publisher
    ..We therefore propose that gene expression changes in palatal shelf mesenchyme that lead to reduced Tgf? signaling contribute to cleft palate in Foxf2(-)(/)(-) mice. ..
  40. Abe S, Abe K, Zhang J, Harada T, Mizumoto G, Oshikawa H, et al. Roles of CD34+ cells and ALK5 signaling in the reconstruction of seminiferous tubule-like structures in 3-D re-aggregate culture of dissociated cells from neonatal mouse testes. PLoS ONE. 2017;12:e0188705 pubmed publisher
    ..These results indicate that CD34+ cells and signaling through ALK5 play pivotal roles in the morphogenesis of interstitial-like, peritubular-like and cord-like structures.
  41. Gokoffski K, Wu H, Beites C, Kim J, Kim E, Matzuk M, et al. Activin and GDF11 collaborate in feedback control of neuroepithelial stem cell proliferation and fate. Development. 2011;138:4131-42 pubmed publisher
    ..Thus, our findings demonstrate a close connection between the signals involved in the control of tissue size and those that regulate the proportions of different cell types...
  42. Yi J, Shin I, Arteaga C. Type I transforming growth factor beta receptor binds to and activates phosphatidylinositol 3-kinase. J Biol Chem. 2005;280:10870-6 pubmed
    ..The interaction of TbetaRI with p85 was induced by treatment with TGFbeta...
  43. Takahashi T, Takahashi K, St John P, Fleming P, Tomemori T, Watanabe T, et al. A mutant receptor tyrosine phosphatase, CD148, causes defects in vascular development. Mol Cell Biol. 2003;23:1817-31 pubmed
    ..These findings implicate a member of the receptor tyrosine phosphatase family, CD148, in developmental vascular organization and provide evidence that it regulates endothelial proliferation and endothelium-pericyte interactions. ..
  44. Komuta Y, Teng X, Yanagisawa H, Sango K, Kawamura K, Kawano H. Expression of transforming growth factor-beta receptors in meningeal fibroblasts of the injured mouse brain. Cell Mol Neurobiol. 2010;30:101-11 pubmed publisher
    ..These results indicate that meningeal fibroblasts not reactive astrocytes are a major target of TGF-beta1 that is upregulated after CNS injury. ..
  45. Roelen B, Goumans M, Zwijsen A, Mummery C. Identification of two distinct functions for TGF-beta in early mouse development. Differentiation. 1998;64:19-31 pubmed
  46. Zhang X, Chang A, Li Y, Gao Y, Wang H, Ma Z, et al. miR-140-5p regulates adipocyte differentiation by targeting transforming growth factor-β signaling. Sci Rep. 2015;5:18118 pubmed publisher
    ..Transforming growth factor-β receptor I (Tgfbr1) was shown to be a direct target of miR-140-5p...
  47. Agrotis A, Samuel M, Prapas G, Bobik A. Vascular smooth muscle cells express multiple type I receptors for TGF-beta, activin, and bone morphogenetic proteins. Biochem Biophys Res Commun. 1996;219:613-8 pubmed
    ..Our finding that multiple ALKs are expressed by VSMCs would account for the multiplicity of effects TGF-beta peptides exert on these cells. ..
  48. Iwata J, Suzuki A, Pelikan R, Ho T, Chai Y. Noncanonical transforming growth factor ? (TGF?) signaling in cranial neural crest cells causes tongue muscle developmental defects. J Biol Chem. 2013;288:29760-70 pubmed publisher
    ..Thus, our data indicate that CNC-derived fibroblasts regulate the fate of mesoderm-derived myoblasts through TGF?-mediated regulation of FGF and BMP signaling during tongue development. ..
  49. Luckett Chastain L, Cottrell M, Kawar B, Ihnat M, Gallucci R. Interleukin (IL)-6 modulates transforming growth factor-? receptor I and II (TGF-?RI and II) function in epidermal keratinocytes. Exp Dermatol. 2017;26:697-704 pubmed publisher
    ..These results suggest that IL-6 regulates keratinocyte function by modulating TGF-?RI and II expression and signal transduction via trafficking of the receptor to lipid raft pools. ..
  50. Wu C, Thalhamer T, Franca R, Xiao S, Wang C, Hotta C, et al. Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells. Immunity. 2014;41:270-82 pubmed publisher
    ..Our data suggest that exogenous galectin-9, in addition to being an effector molecule for Treg cells, acts synergistically with TGF-? to enforce iTreg cell differentiation and maintenance. ..
  51. Konkel J, Maruyama T, Carpenter A, Xiong Y, Zamarron B, Hall B, et al. Control of the development of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β. Nat Immunol. 2011;12:312-9 pubmed publisher
    ..Our data demonstrate a previously unrecognized role for TGF-β in the development of TCRαβ+CD8αα+ IELs and the expression of CD8α in T cells. ..
  52. Ho Y, Tsai W, Lin F, Huang W, Lin L, Wu S, et al. Cardioprotective Actions of TGFβRI Inhibition Through Stimulating Autocrine/Paracrine of Survivin and Inhibiting Wnt in Cardiac Progenitors. Stem Cells. 2016;34:445-55 pubmed publisher
    ..TGFβRI inhibition in an injured adult heart could both stimulate the autocrine/paracrine activity of survivin and inhibit Wnt in CPCs to mediate cardioprotection and improve cardiac function. ..
  53. Larsson J, Blank U, Helgadottir H, Bjornsson J, Ehinger M, Goumans M, et al. TGF-beta signaling-deficient hematopoietic stem cells have normal self-renewal and regenerative ability in vivo despite increased proliferative capacity in vitro. Blood. 2003;102:3129-35 pubmed
    ..These findings challenge the classical view that TGF-beta is an essential negative regulator of hematopoietic stem cells under physiologic conditions in vivo. ..
  54. Kang J, Saunier E, Akhurst R, Derynck R. The type I TGF-beta receptor is covalently modified and regulated by sumoylation. Nat Cell Biol. 2008;10:654-64 pubmed publisher
    ..T beta RI sumoylation therefore controls responsiveness to TGF-beta, with implications for tumour progression. Sumoylation of cell-surface receptors may regulate other growth factor responses. ..
  55. King A, Clarkin C, Austin A, Ajram L, Dhunna J, Jamil M, et al. ALK5 inhibition maintains islet endothelial cell survival but does not enhance islet graft revascularisation or function. Horm Metab Res. 2015;47:78-83 pubmed publisher
    ..The ALK5 pathway inhibits endothelial cell proliferation and thus inhibiting ALK5 is a potential target for improving ..
  56. del Re E, Babitt J, Pirani A, Schneyer A, Lin H. In the absence of type III receptor, the transforming growth factor (TGF)-beta type II-B receptor requires the type I receptor to bind TGF-beta2. J Biol Chem. 2004;279:22765-72 pubmed
    ..factor beta (TGF-beta) ligands exert their biological effects through type II (TbetaRII) and type I receptors (TbetaRI)...
  57. Kim S, Kwak J, Na H, Kim J, Ding Y, Choi M. Transforming growth factor-beta (TGF-beta1) activates TAK1 via TAB1-mediated autophosphorylation, independent of TGF-beta receptor kinase activity in mesangial cells. J Biol Chem. 2009;284:22285-96 pubmed publisher
    ..growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that signals through the interaction of type I (TbetaRI) and type II (TbetaRII) receptors to activate distinct intracellular pathways...
  58. Dünker N, Krieglstein K. Reduced programmed cell death in the retina and defects in lens and cornea of Tgfbeta2(-/-) Tgfbeta3(-/-) double-deficient mice. Cell Tissue Res. 2003;313:1-10 pubmed
    ..Moreover, our data indicate that TGF-betas play essential roles in cornea and lens development. ..
  59. Guo H, Kazadaeva Y, Ortega F, Manjunath N, Desai T. Trinucleotide repeat containing 6c (TNRC6c) is essential for microvascular maturation during distal airspace sacculation in the developing lung. Dev Biol. 2017;430:214-223 pubmed publisher
    ..These results imply a complex and indirect mode of regulation of sacculation by TNRC6c, mediated in part by dynamic transcriptional repression of an inhibitor of TGF? family gene expression. ..
  60. Liu W, Rui H, Wang J, Lin S, He Y, Chen M, et al. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 2006;25:1646-58 pubmed
    ..However, coexpression of Wnt-1 reduced Smad7 ubiquitination by downregulating Axin levels, underscoring the importance of Axin as an intrinsic regulator in TGF-beta signaling. ..
  61. Okano J, Takigawa T, Seki K, Suzuki S, Shiota K, Ishibashi M. Transforming growth factor beta 2 promotes the formation of the mouse cochleovestibular ganglion in organ culture. Int J Dev Biol. 2005;49:23-31 pubmed
    ..Addition of TGFbeta2 peptide to the culture led to Enlargement of the CVG, while the inhibitor reduced its size. These findings strongly imply that TGFbeta2 contributes to the development of the CVG in mouse embryos. ..
  62. Smoktunowicz N, Alexander R, Franklin L, Williams A, Holman B, Mercer P, et al. The anti-fibrotic effect of inhibition of TGFβ-ALK5 signalling in experimental pulmonary fibrosis in mice is attenuated in the presence of concurrent γ-herpesvirus infection. Dis Model Mech. 2015;8:1129-39 pubmed publisher
    TGFβ-ALK5 pro-fibrotic signalling and herpesvirus infections have been implicated in the pathogenesis and exacerbation of pulmonary fibrosis...
  63. Bai Y, Yang C, Hu K, Elly C, Liu Y. Itch E3 ligase-mediated regulation of TGF-beta signaling by modulating smad2 phosphorylation. Mol Cell. 2004;15:825-31 pubmed
    ..This study reveals a previously unrecognized positive TGF-beta signaling pathway via proteolysis-independent ubiquitination. ..
  64. Dudas M, Nagy A, Laping N, Moustakas A, Kaartinen V. Tgf-beta3-induced palatal fusion is mediated by Alk-5/Smad pathway. Dev Biol. 2004;266:96-108 pubmed
    ..Based on these observations, we conclude that the Smad2-dependent Alk-5 signaling pathway is dominant in palatal fusion driven by Tgf-beta3. ..
  65. Li Q, Agno J, Edson M, Nagaraja A, Nagashima T, Matzuk M. Transforming growth factor ? receptor type 1 is essential for female reproductive tract integrity and function. PLoS Genet. 2011;7:e1002320 pubmed publisher
    ..TGF? type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is the major type 1 receptor for TGF? ligands...
  66. Liu J, Johnson K, Li J, Piamonte V, Steffy B, Hsieh M, et al. Regenerative phenotype in mice with a point mutation in transforming growth factor beta type I receptor (TGFBR1). Proc Natl Acad Sci U S A. 2011;108:14560-5 pubmed publisher
    ..This trait was mapped to a point mutation in a receptor for TGF-?, TGFBR1. Mouse embryonic fibroblasts from the affected mice had increased expression of a subset of TGF-? target genes, ..
  67. Xiao L, Peng X, Liu F, Tang C, Hu C, Xu X, et al. AKT regulation of mesothelial-to-mesenchymal transition in peritoneal dialysis is modulated by Smurf2 and deubiquitinating enzyme USP4. BMC Cell Biol. 2015;16:7 pubmed publisher
    ..These data implied that Akt mediated MMT in PD via Smurf2 modulation/and or Smad7 degradation while conceivably maintaining the TβRI stability, most likely by the USP4. ..
  68. O Brien C, Bonanno L, Zhang H, Wyss Coray T. Beclin 1 regulates neuronal transforming growth factor-β signaling by mediating recycling of the type I receptor ALK5. Mol Neurodegener. 2015;10:69 pubmed publisher
    ..Beclin 1 is required for recycling of the type I TGF-β receptor ALK5. We show that beclin 1 recruits the retromer to ALK5 and facilitates its localization to Rab11(+) endosomes...
  69. Yamazaki S, Iwama A, Takayanagi S, Eto K, Ema H, Nakauchi H. TGF-beta as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation. Blood. 2009;113:1250-6 pubmed publisher
    ..These data uncover a critical role for TGF-beta as a candidate niche signal in the control of HSC hibernation and provide TGF-beta as a novel tool for ex vivo modeling of the HSC niche. ..
  70. Lu Y, Lin Y, Kao Y, Chung C, Yeh Y, Chen S, et al. Collagen regulates transforming growth factor-? receptors of HL-1 cardiomyocytes through activation of stretch and integrin signaling. Mol Med Rep. 2016;14:3429-36 pubmed publisher
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    ..Thus, our study reveals a previously unrecognized TAK1-Id3-E2A-GATA-3 pathway that regulates TH9 differentiation. ..
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    ..Inhibition of signaling through the receptors ALK4, ALK5 and ALK7, and ALK5 alone, demonstrated that TGF? signaling is required for testis cord formation during the ..
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    ..In certain cell types, in addition to the canonical type I receptor, ALK5, which activates Smad2/3, TGF-? can signal through another type I receptor, ALK1, which activates Smad1/5...
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    ..These and other findings provide insight into the design of future functional studies. ..
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