Genomes and Genes
Gene Symbol: Tgfbr2
Description: transforming growth factor, beta receptor II
Alias: 1110020H15Rik, AU042018, DNIIR, RIIDN, TBR-II, TbetaR-II, TbetaRII, TGF-beta receptor type-2, TGF-beta receptor II, TGF-beta receptor type II, TGF-beta type II receptor, TGFR-2, transforming growth factor-beta receptor type II
- Chai Y, Zhao J, Mogharei A, Xu B, Bringas P, Shuler C, et al. Inhibition of transforming growth factor-beta type II receptor signaling accelerates tooth formation in mouse first branchial arch explants. Mech Dev. 1999;86:63-74 pubmed
- Schadt E, Lamb J, Yang X, Zhu J, Edwards S, GuhaThakurta D, et al. An integrative genomics approach to infer causal associations between gene expression and disease. Nat Genet. 2005;37:710-7 pubmed..We also demonstrate the utility of this approach by identifying and experimentally validating the involvement of three new genes in susceptibility to obesity. ..
- Sasaki T, Ito Y, Bringas P, Chou S, Urata M, Slavkin H, et al. TGFbeta-mediated FGF signaling is crucial for regulating cranial neural crest cell proliferation during frontal bone development. Development. 2006;133:371-81 pubmed..Our previous study has demonstrated that conditional inactivation of Tgfbr2 in the neural crest results in severe defects in calvarial development, although the cellular and molecular ..
- 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. ..
- Ouyang W, Beckett O, Ma Q, Li M. Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. Immunity. 2010;32:642-53 pubmed publisher..These findings reveal a critical function for TGF-beta in control of autoreactive T cell fates with important implications for understanding T cell self-tolerance mechanisms. ..
- Serra R, Johnson M, Filvaroff E, LaBorde J, Sheehan D, Derynck R, et al. Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J Cell Biol. 1997;139:541-52 pubmed..can compete with the endogenous receptors for complex formation, thereby acting as a dominant-negative mutant (DNIIR)...
- Leveen P, Larsson J, Ehinger M, Cilio C, Sundler M, Sjöstrand L, et al. Induced disruption of the transforming growth factor beta type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable. Blood. 2002;100:560-8 pubmed..phenotype would develop following transplantation of bone marrow deficient for the TGF-beta type II receptor (TbetaRII) gene to normal recipient animals...
- Ijichi H, Chytil A, Gorska A, Aakre M, Bierie B, Tada M, et al. Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma. J Clin Invest. 2011;121:4106-17 pubmed publisher..We previously generated pancreas epithelium-specific TGF-? receptor type II (Tgfbr2) knockout mice in the context of Kras activation (mice referred to herein as Kras+Tgfbr2KO mice) and found that ..
- Baffi M, Slattery E, Sohn P, Moses H, Chytil A, Serra R. Conditional deletion of the TGF-beta type II receptor in Col2a expressing cells results in defects in the axial skeleton without alterations in chondrocyte differentiation or embryonic development of long bones. Dev Biol. 2004;276:124-42 pubmed..in skeletal development, we generated mice with a conditional deletion of the TGF-beta type II receptor gene (Tgfbr2) specifically in Col2a expressing cells using the Cre/lox recombinase system...
- Clotman F, Jacquemin P, Plumb Rudewiez N, Pierreux C, Van Der Smissen P, Dietz H, et al. Control of liver cell fate decision by a gradient of TGF beta signaling modulated by Onecut transcription factors. Genes Dev. 2005;19:1849-54 pubmed..Thus, a gradient of activin/TGFbeta signaling modulated by Onecut factors is required to segregate the hepatocytic and the biliary lineages. ..
- 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 as mouse ..
- Hirota S, Liu Q, Lee H, Hossain M, Lacy Hulbert A, McCarty J. The astrocyte-expressed integrin ?v?8 governs blood vessel sprouting in the developing retina. Development. 2011;138:5157-66 pubmed publisher..Collectively, our data demonstrate that ?v?8 integrin is a component of a paracrine signaling axis that links astrocytes to blood vessels and is essential for proper regulation of retinal angiogenesis. ..
- Seo H, Serra R. Deletion of Tgfbr2 in Prx1-cre expressing mesenchyme results in defects in development of the long bones and joints. Dev Biol. 2007;310:304-16 pubmedIn this study, we address the function of Transforming Growth Factor beta (TGF-beta) and its type II receptor (Tgfbr2) in limb development in vivo...
- Wang X, Greenhalgh D, Bickenbach J, Jiang A, Bundman D, Krieg T, et al. Expression of a dominant-negative type II transforming growth factor beta (TGF-beta) receptor in the epidermis of transgenic mice blocks TGF-beta-mediated growth inhibition. Proc Natl Acad Sci U S A. 1997;94:2386-91 pubmed..These data document the role of the type II TGF-beta receptor in mediating TGF-beta-induced growth inhibition of the epidermis in vivo and in maintenance of epidermal homeostasis. ..
- 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..TGFbeta type II receptor is also required for ALK1 activation by TGFbeta. Interestingly, ALK1 not only induces a biological response opposite to that of ALK5 but also directly antagonizes ALK5/Smad signaling. ..
- Robson A, Allinson K, Anderson R, Henderson D, Arthur H. The TGF? type II receptor plays a critical role in the endothelial cells during cardiac development. Dev Dyn. 2010;239:2435-42 pubmed publisher..Atrioventricular-myocardial-specific Tgfbr2 knockout (KO) embryos had short septal leaflets of the tricuspid valve, whereas ventricular myocardial-specific KO ..
- Ramalingam R, Larmonier C, Thurston R, Midura Kiela M, Zheng S, Ghishan F, et al. Dendritic cell-specific disruption of TGF-? receptor II leads to altered regulatory T cell phenotype and spontaneous multiorgan autoimmunity. J Immunol. 2012;189:3878-93 pubmed publisher..previously in vitro, we generated conditional knockout (KO) mice with Cre-mediated DC-specific deletion of Tgfbr2 (DC-Tgfbr2 KO)...
- Antoniou A, Raynaud P, Cordi S, Zong Y, Tronche F, Stanger B, et al. Intrahepatic bile ducts develop according to a new mode of tubulogenesis regulated by the transcription factor SOX9. Gastroenterology. 2009;136:2325-33 pubmed publisher..In the embryo, hepatoblasts differentiate to cholangiocytes, which give rise to the bile ducts. Here, we investigated duct development in mouse liver and characterized the role of the SRY-related HMG box transcription factor 9 (SOX9)...
- 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. ..
- 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...
- Chytil A, Magnuson M, Wright C, Moses H. Conditional inactivation of the TGF-beta type II receptor using Cre:Lox. Genesis. 2002;32:73-5 pubmed
- Li M, Sanjabi S, Flavell R. Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity. 2006;25:455-71 pubmed..This study reveals pleiotropic functions of TGF-beta signaling in T cells that may ensure a diverse and self-tolerant T cell repertoire in vivo. ..
- Chen C, Liu I, Fliesler S, Han X, Huang S, Huang J. Cholesterol suppresses cellular TGF-beta responsiveness: implications in atherogenesis. J Cell Sci. 2007;120:3509-21 pubmed..These results suggest that high cholesterol contributes to atherogenesis, at least in part, by suppressing TGF-beta responsiveness in vascular cells. ..
- Lawler S, Candia A, Ebner R, Shum L, Lopez A, Moses H, et al. The murine type II TGF-beta receptor has a coincident embryonic expression and binding preference for TGF-beta 1. Development. 1994;120:165-75 pubmed
- Taya Y, O Kane S, Ferguson M. Pathogenesis of cleft palate in TGF-beta3 knockout mice. Development. 1999;126:3869-79 pubmed
- 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..We directly addressed these issues in vivo by comparing the phenotypes of mice in which the Alk1, Alk5, or Tgfbr2 gene was conditionally deleted in restricted vascular endothelia using a novel endothelial Cre transgenic line...
- 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. ..
- Choudhary B, Ito Y, Makita T, Sasaki T, Chai Y, Sucov H. Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFbeta receptor (Tgfbr2) mutant mice. Dev Biol. 2006;289:420-9 pubmed..We infer that TGFbeta is an essential morphogenic signal for the neural crest cell lineage in specific aspects of cardiovascular development, although one that is not required for smooth muscle differentiation...
- Weiss J, Bilate A, Gobert M, Ding Y, Curotto de Lafaille M, Parkhurst C, et al. Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. J Exp Med. 2012;209:1723-42, S1 pubmed..In the same animals, iT reg cells in secondary lymphoid organs remain Nrp1(low). We also determined that, in spontaneous EAE, iT reg cells help to establish a chronic phase of the disease...
- PLACENCIO V, Sharif Afshar A, Li X, Huang H, Uwamariya C, Neilson E, et al. Stromal transforming growth factor-beta signaling mediates prostatic response to androgen ablation by paracrine Wnt activity. Cancer Res. 2008;68:4709-18 pubmed publisher..response to androgen ablation, conditional TGF-beta type II receptor knockout mouse models of the epithelia (Tgfbr2(NKX3.1KO)) and stromal fibroblasts (Tgfbr2(fspKO)) were used. After castration, the prostates of Tgfbr2(NKX3...
- Plumb Rudewiez N, Clotman F, Strick Marchand H, Pierreux C, Weiss M, Rousseau G, et al. Transcription factor HNF-6/OC-1 inhibits the stimulation of the HNF-3alpha/Foxa1 gene by TGF-beta in mouse liver. Hepatology. 2004;40:1266-74 pubmed..This identifies a new mechanism of interaction between liver-enriched transcription factors whereby one factor indirectly controls another by modulating the activity of a signaling pathway. ..
- Dunker N, Krieglstein K. Targeted mutations of transforming growth factor-beta genes reveal important roles in mouse development and adult homeostasis. Eur J Biochem. 2000;267:6982-8 pubmed..5. Together, gene ablation within the TGF-beta signalling pathway supports the notion of a prominent role of TGF-beta during development. ..
- 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
- 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. ..
- Oshima M, Oshima H, Taketo M. TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev Biol. 1996;179:297-302 pubmed..To determine the role of TGF-betaRII in embryogenesis, we have generated a TGF-betaRII gene (Tgfbr2) knockout mouse line. The heterozygous Tgfbr2 knockout mice are developmentally normal...
- Doisne J, Bartholin L, Yan K, Garcia C, Duarte N, Le Luduec J, et al. iNKT cell development is orchestrated by different branches of TGF-beta signaling. J Exp Med. 2009;206:1365-78 pubmed publisher..Thus, these three different branches of TGF-beta signaling function in concert as complementary effectors, allowing TGF-beta to fine tune the iNKT cell differentiation program. ..
- Arnold T, Ferrero G, Qiu H, Phan I, Akhurst R, Huang E, et al. Defective retinal vascular endothelial cell development as a consequence of impaired integrin ?V?8-mediated activation of transforming growth factor-?. J Neurosci. 2012;32:1197-206 pubmed publisher..Of special interest, the retinal vascular phenotypes observed in each mutant are remarkably similar to those of others following inhibition of neuropilin-1, a receptor previously implicated in TGF? activation and signaling. ..
- Pryce B, Watson S, Murchison N, Staverosky J, Dünker N, Schweitzer R. Recruitment and maintenance of tendon progenitors by TGFbeta signaling are essential for tendon formation. Development. 2009;136:1351-61 pubmed publisher..double mutant embryos or through inactivation of the type II TGFbeta receptor (TGFBR2; also known as TbetaRII) results in the loss of most tendons and ligaments in the limbs, trunk, tail and head...
- Jiao K, Langworthy M, Batts L, Brown C, Moses H, Baldwin H. Tgfbeta signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development. Development. 2006;133:4585-93 pubmed..To understand the role(s) of Tgfbeta signaling during cardiogenesis in vivo and to overcome the early lethality of Tgfbr2(-/-) embryos, we applied a Cre/loxp system to specifically inactivate Tgfbr2 in either the myocardium or the ..
- 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. ..
- 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..We report that deletion of Tgfbr2 in the neuroepithelium does not impact brain vascular development...
- Mariano J, Montuenga L, Prentice M, Cuttitta F, Jakowlew S. Concurrent and distinct transcription and translation of transforming growth factor-beta type I and type II receptors in rodent embryogenesis. Int J Dev Biol. 1998;42:1125-36 pubmed..These data show that regulation of TGF-beta1 RI and RII occurs concurrently, but distinctly, in a spatial and temporal manner in rodent embryogenesis which may allow control of signal transduction of TGF-beta during development. ..
- Zhang N, Bevan M. TGF-? signaling to T cells inhibits autoimmunity during lymphopenia-driven proliferation. Nat Immunol. 2012;13:667-73 pubmed publisher..We propose that TGF-? signaling controls the self-reactivity of peripheral T cells but that in the absence of TGF-? signals, an added trigger such as lymphopenia is needed to drive overt autoimmune disease. ..
- Xu X, Han J, Ito Y, Bringas P, Urata M, Chai Y. Cell autonomous requirement for Tgfbr2 in the disappearance of medial edge epithelium during palatal fusion. Dev Biol. 2006;297:238-48 pubmed..By using the Cre/lox system, we are able to label the MEE genetically and to ablate Tgfbr2 specifically in the palatal epithelial cells...
- Miyabayashi K, Ijichi H, Mohri D, Tada M, Yamamoto K, Asaoka Y, et al. Erlotinib prolongs survival in pancreatic cancer by blocking gemcitabine-induced MAPK signals. Cancer Res. 2013;73:2221-34 pubmed publisher..gemcitabine alone in blocking progression and prolonging survival in a murine model of PDAC (Kras activation with Tgfbr2 knockout)...
- Li X, PLACENCIO V, Iturregui J, Uwamariya C, Sharif Afshar A, Koyama T, et al. Prostate tumor progression is mediated by a paracrine TGF-beta/Wnt3a signaling axis. Oncogene. 2008;27:7118-30 pubmed publisher..In mice, the conditional stromal knockout of the TGF-beta type II receptor expression (Tgfbr2(fspKO)) resulted in the development of prostatic intraepithelial neoplasia and progression to adenocarcinoma ..
- Bhowmick N, Chytil A, Plieth D, Gorska A, Dumont N, Shappell S, et al. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science. 2004;303:848-51 pubmed..Thus, TGF-beta signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues. ..
- Marie J, Liggitt D, Rudensky A. Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity. 2006;25:441-54 pubmed..Thus, TGF-beta signaling in peripheral T cells is crucial in restraining TCR activation-dependent Th1, cytotoxic, and NK cell-like differentiation program which, when left unchecked, leads to rapidly progressing fatal autoimmunity. ..
- 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..Remarkable divergence between Tgfbr2 and Alk5 phenotypes, together with our biochemical in vitro data, imply that (1) ALK5 mediates signaling of a ..
- Leveen P, Carlsén M, Makowska A, Oddsson S, Larsson J, Goumans M, et al. TGF-beta type II receptor-deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo. Blood. 2005;106:4234-40 pubmed..system to generate a mouse model with inducible deficiency of transforming growth factor beta receptor II (TbetaRII)...