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Gene Review

Tgfbr2  -  transforming growth factor, beta receptor II

Mus musculus

Synonyms: 1110020H15Rik, AU042018, DNIIR, RIIDN, TBR-II, ...
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Disease relevance of Tgfbr2

  • Loss of Tgfbr2 in the mammary epithelium results in lobular-alveolar hyperplasia in the developing mammary gland and increased apoptosis [1].
  • Cleft palate in Tgfbr2 mutant mice results from a cell proliferation defect within the CNC-derived palatal mesenchyme [2].
  • To assess the functional role of TGFBR2 inactivation in the multistep progression sequence of colon cancer, we generated a mouse model that recapitulates two common genetic events observed in human colon cancer by mating Apc(1638N/wt) mice with mice that are null for Tgfbr2 in the intestinal epithelium, Villin-Cre;Tgfbr2(E2flx/E2flx) mice [3].
  • In this model, we observed a dramatic increase in the number of intestinal adenocarcinomas in the Apc(1638N/wt);Villin-Cre;Tgfbr2(E2flx/E2flx) mice (called Apc(1638N/wt);Tgfbr2(IEKO)) compared with those mice with intact Tgfbr2 (Apc(1638N/wt);Tgfbr2(E2flx/E2flx)) [3].
  • Loss of Tgfbr2 in the context of PyVmT expression results in a shortened median tumor latency and an increased formation of pulmonary metastases [1].

High impact information on Tgfbr2


Chemical compound and disease context of Tgfbr2

  • By mating Fabpl(4xat-132) Cre mice with Tgfbr2(flx/flx) mice, we have generated a mouse model that is null for Tgfbr2 in the colonic epithelium, and in this model system, we have assessed the effect of loss of TGF-beta signaling in vivo on colon cancer formation induced by azoxymethane (AOM) [8].
  • Taken together, these data for the first time demonstrated a role for RA-induced hypochondrogenesis through regulation of the TGF-beta3 pathway and suggested a role for TbetaRII /Smad in retinoid-induced cleft palate [9].
  • These data provide evidence for a cholesterol-dependent TbetaR-II induction that may play a potentially relevant role in the development of hypercholesterolemia and atherogenesis [10].
  • In addition, the in vivo effects of TbetaRII siRNA were evaluated in a mouse model of ocular inflammation and fibrosis generated by subconjunctival injection of phosphate buffered saline and latex beads [11].

Biological context of Tgfbr2


Anatomical context of Tgfbr2

  • Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects [2].
  • Hepatocytes isolated from liver-specific Tgfbr2 knockout (R2LivKO) mice were refractory to the growth inhibitory effects of TGF-beta1 [15].
  • 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 mechanisms by which TGFbeta signaling regulates the fate of CNC cells during frontal bone development remain unknown [16].
  • However, this requirement is restricted to the developing calvarial aspect of the frontal bone, whereas the orbital aspect forms despite the ablation of Tgfbr2 gene, implying a differential requirement for TGFbeta signaling during the development of various regions of the frontal bone [16].
  • Consequently, we have developed a hepatocyte-specific Tgfbr2 knockout mouse, the Alb-cre Tgfbr2(flx/flx) mouse, to study the physiologically relevant effects of TGF-beta signaling on epithelial cell proliferation in vivo [17].

Associations of Tgfbr2 with chemical compounds


Physical interactions of Tgfbr2


Regulatory relationships of Tgfbr2

  • The TbetaRII-null mutation would generate a cell autonomous phenotype that cannot be reverted by the influence of endocrine or paracrine TGF-beta derived from the recipient animal [25].
  • METHODS: In the present study, we examined whether decreased expression of the TGF-beta type II receptor (TGF-betaIIR) in TGF-betaIIR gene heterozygous (TGF-betaIIR+/-) (HT) mice could inhibit the Smad signaling pathway and subsequent progression of renal lesions when streptozotocin (STZ) diabetes is induced [26].
  • Expression of dominant negative TbetaRII in goblet cells greatly inhibited the conversion of the beta1 integrin from its precursor to its mature form [27].
  • In contrast, PEA3 stimulates the TbetaR-II promoter in F9-differentiated cells, but it inhibits this promoter in F9 cells [28].
  • After orthotopic transplantation to the floor of the mouth in athymic mice, cells containing dn TbetaR-II formed comparable numbers of primary tumours at the site of inoculation as controls but the tumours were less differentiated as demonstrated by the absence of keratin 10 immunostaining [29].

Other interactions of Tgfbr2


Analytical, diagnostic and therapeutic context of Tgfbr2


  1. Effect of conditional knockout of the type II TGF-beta receptor gene in mammary epithelia on mammary gland development and polyomavirus middle T antigen induced tumor formation and metastasis. Forrester, E., Chytil, A., Bierie, B., Aakre, M., Gorska, A.E., Sharif-Afshar, A.R., Muller, W.J., Moses, H.L. Cancer Res. (2005) [Pubmed]
  2. Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects. Ito, Y., Yeo, J.Y., Chytil, A., Han, J., Bringas, P., Nakajima, A., Shuler, C.F., Moses, H.L., Chai, Y. Development (2003) [Pubmed]
  3. Transforming Growth Factor {beta} Receptor Type II Inactivation Induces the Malignant Transformation of Intestinal Neoplasms Initiated by Apc Mutation. Mu??oz, N.M., Upton, M., Rojas, A., Washington, M.K., Lin, L., Chytil, A., Sozmen, E.G., Madison, B.B., Pozzi, A., Moon, R.T., Moses, H.L., Grady, W.M. Cancer Res. (2006) [Pubmed]
  4. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Ijichi, H., Chytil, A., Gorska, A.E., Aakre, M.E., Fujitani, Y., Fujitani, S., Wright, C.V., Moses, H.L. Genes Dev. (2006) [Pubmed]
  5. Concerted action of TGF-beta 1 and its type II receptor in control of epidermal homeostasis in transgenic mice. Cui, W., Fowlis, D.J., Cousins, F.M., Duffie, E., Bryson, S., Balmain, A., Akhurst, R.J. Genes Dev. (1995) [Pubmed]
  6. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Gorelik, L., Flavell, R.A. Immunity (2000) [Pubmed]
  7. TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo. Cazac, B.B., Roes, J. Immunity (2000) [Pubmed]
  8. Transforming growth factor beta receptor type II inactivation promotes the establishment and progression of colon cancer. Biswas, S., Chytil, A., Washington, K., Romero-Gallo, J., Gorska, A.E., Wirth, P.S., Gautam, S., Moses, H.L., Grady, W.M. Cancer Res. (2004) [Pubmed]
  9. All-trans retinoic acid inhibited chondrogenesis of mouse embryonic palate mesenchymal cells by down-regulation of TGF-beta/Smad signaling. Yu, Z., Xing, Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  10. Increased type II transforming growth factor-beta receptor expression in liver cells during cholesterol challenge. Baccante, G., Mincione, G., Di Febbo, C., Coppa, A., Angelucci, D., Lapenna, D., Cuccurullo, F., Colletta, G., Porreca, E. Atherosclerosis (2000) [Pubmed]
  11. RNA interference targeting transforming growth factor-beta type II receptor suppresses ocular inflammation and fibrosis. Nakamura, H., Siddiqui, S.S., Shen, X., Malik, A.B., Pulido, J.S., Kumar, N.M., Yue, B.Y. Mol. Vis. (2004) [Pubmed]
  12. TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Oshima, M., Oshima, H., Taketo, M.M. Dev. Biol. (1996) [Pubmed]
  13. Constitutive homo- and hetero-oligomerization of TbetaRII-B, an alternatively spliced variant of the mouse TGF-beta type II receptor. Krishnaveni, M.S., Hansen, J.L., Seeger, W., Morty, R.E., Sheikh, S.P., Eickelberg, O. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  14. Heterozygous mice for the transforming growth factor-beta type II receptor gene have increased susceptibility to hepatocellular carcinogenesis. Im, Y.H., Kim, H.T., Kim, I.Y., Factor, V.M., Hahm, K.B., Anzano, M., Jang, J.J., Flanders, K., Haines, D.C., Thorgeirsson, S.S., Sizeland, A., Kim, S.J. Cancer Res. (2001) [Pubmed]
  15. Intact signaling by transforming growth factor beta is not required for termination of liver regeneration in mice. Oe, S., Lemmer, E.R., Conner, E.A., Factor, V.M., Levéen, P., Larsson, J., Karlsson, S., Thorgeirsson, S.S. Hepatology (2004) [Pubmed]
  16. TGFbeta-mediated FGF signaling is crucial for regulating cranial neural crest cell proliferation during frontal bone development. Sasaki, T., Ito, Y., Bringas, P., Chou, S., Urata, M.M., Slavkin, H., Chai, Y. Development (2006) [Pubmed]
  17. Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy. Romero-Gallo, J., Sozmen, E.G., Chytil, A., Russell, W.E., Whitehead, R., Parks, W.T., Holdren, M.S., Her, M.F., Gautam, S., Magnuson, M., Moses, H.L., Grady, W.M. Oncogene (2005) [Pubmed]
  18. Estrogen-induced tumorigenesis in the pituitary gland of TGF-beta(+/-) knockout mice. Shida, N., Ikeda, H., Yoshimoto, T., Oshima, M., Taketo, M.M., Miyoshi, I. Biochim. Biophys. Acta (1998) [Pubmed]
  19. TGF-beta type II receptor-deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo. Levéen, P., Carlsén, M., Makowska, A., Oddsson, S., Larsson, J., Goumans, M.J., Cilio, C.M., Karlsson, S. Blood (2005) [Pubmed]
  20. Changes in levels of mRNAs of transforming growth factor (TGF)-beta1, -beta2, -beta3, TGF-beta type II receptor and sulfated glycoprotein-2 during apoptosis of mouse uterine epithelium. Wada, K., Nomura, S., Morii, E., Kitamura, Y., Nishizawa, Y., Miyake, A., Terada, N. J. Steroid Biochem. Mol. Biol. (1996) [Pubmed]
  21. Expression of TGF-beta s and TGF-beta type II receptor mRNAs in mouse folliculogenesis: stored maternal TGF-beta 2 message in oocytes. Schmid, P., Cox, D., van der Putten, H., McMaster, G.K., Bilbe, G. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  22. Effects of high glucose and TGF-beta1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes. Iglesias-de la Cruz, M.C., Ziyadeh, F.N., Isono, M., Kouahou, M., Han, D.C., Kalluri, R., Mundel, P., Chen, S. Kidney Int. (2002) [Pubmed]
  23. Disruption of transforming growth factor beta signaling by a novel ligand-dependent mechanism. Fernandez, T., Amoroso, S., Sharpe, S., Jones, G.M., Bliskovski, V., Kovalchuk, A., Wakefield, L.M., Kim, S.J., Potter, M., Letterio, J.J. J. Exp. Med. (2002) [Pubmed]
  24. Assembly of TbetaRI:TbetaRII:TGFbeta ternary complex in vitro with receptor extracellular domains is cooperative and isoform-dependent. Zúñiga, J.E., Groppe, J.C., Cui, Y., Hinck, C.S., Contreras-Shannon, V., Pakhomova, O.N., Yang, J., Tang, Y., Mendoza, V., López-Casillas, F., Sun, L., Hinck, A.P. J. Mol. Biol. (2005) [Pubmed]
  25. Induced disruption of the transforming growth factor beta type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable. Levéen, P., Larsson, J., Ehinger, M., Cilio, C.M., Sundler, M., Sjöstrand, L.J., Holmdahl, R., Karlsson, S. Blood (2002) [Pubmed]
  26. Heterozygous mice for TGF-betaIIR gene are resistant to the progression of streptozotocin-induced diabetic nephropathy. Kim, H.W., Kim, B.C., Song, C.Y., Kim, J.H., Hong, H.K., Lee, H.S. Kidney Int. (2004) [Pubmed]
  27. Differential responsiveness to autocrine and exogenous transforming growth factor (TGF) beta1 in cells with nonfunctional TGF-beta receptor type III. Deng, X., Bellis, S., Yan, Z., Friedman, E. Cell Growth Differ. (1999) [Pubmed]
  28. Unique and selective effects of five Ets family members, Elf3, Ets1, Ets2, PEA3, and PU.1, on the promoter of the type II transforming growth factor-beta receptor gene. Kopp, J.L., Wilder, P.J., Desler, M., Kim, J.H., Hou, J., Nowling, T., Rizzino, A. J. Biol. Chem. (2004) [Pubmed]
  29. Attenuated type II TGF-beta receptor signalling in human malignant oral keratinocytes induces a less differentiated and more aggressive phenotype that is associated with metastatic dissemination. Huntley, S.P., Davies, M., Matthews, J.B., Thomas, G., Marshall, J., Robinson, C.M., Eveson, J.W., Paterson, I.C., Prime, S.S. Int. J. Cancer (2004) [Pubmed]
  30. 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. Baffi, M.O., Slattery, E., Sohn, P., Moses, H.L., Chytil, A., Serra, R. Dev. Biol. (2004) [Pubmed]
  31. Restoration of expression of transforming growth factor-beta type II receptor in murine renal cell carcinoma (renca) cells by 5-Aza-2'-deoxycytidine. Zhang, Q., Rubenstein, J.N., Liu, V.C., Park, I., Jang, T., Lee, C. Life Sci. (2005) [Pubmed]
  32. Abrogation of betaglycan attenuates TGF-beta-mediated inhibition of embryonic murine lung branching morphogenesis in culture. P2ao, J., Tefft, J.D., Lee, M., Smith, S., Warburton, D. Mech. Dev. (1998) [Pubmed]
  33. Expression of TGF-beta s and their receptors during implantation and organogenesis of the mouse embryo. Roelen, B.A., Lin, H.Y., Knezević, V., Freund, E., Mummery, C.L. Dev. Biol. (1994) [Pubmed]
  34. Immunohistochemical localization of TGF-beta type II receptor and TGF-beta3 during palatogenesis in vivo and in vitro. Cui, X.M., Warburton, D., Zhao, J., Crowe, D.L., Shuler, C.F. Int. J. Dev. Biol. (1998) [Pubmed]
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