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Gene Review

TGFBR3  -  transforming growth factor, beta receptor III

Homo sapiens

Synonyms: BGCAN, Betaglycan, TGF-beta receptor type 3, TGF-beta receptor type III, TGFR-3, ...
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Disease relevance of TGFBR3


High impact information on TGFBR3

  • Betaglycan presents TGF beta directly to the kinase subunit of the signaling receptor, forming a high affinity ternary complex [5].
  • The transmembrane region and the short cytoplasmic tail of betaglycan are very similar to these regions in human endoglin, an endothelial cell membrane glycoprotein involved in intercellular recognition [6].
  • The unique features of betaglycan suggest important roles in cell interaction with TGF-beta [6].
  • Finally, betaglycan confers inhibin sensitivity to cell lines that otherwise respond poorly to this hormone [7].
  • Most human breast cancers lost TbetaRIII expression, with loss of heterozygosity of the TGFBR3 gene locus correlating with decreased TbetaRIII expression [2].

Chemical compound and disease context of TGFBR3


Biological context of TGFBR3


Anatomical context of TGFBR3


Associations of TGFBR3 with chemical compounds

  • Their mutation to alanine prevents GAG attachment but does not interfere with betaglycan stability or ability to bind and present TGF-beta to receptor II [10].
  • Using a panel of deletion mutants, we found that TGF-beta binds to the NH2-terminal endoglin-related region of betaglycan [10].
  • Here we present evidence showing that in certain cell types, pervanadate, a general tyrosine phosphatase inhibitor, induces the release of the previously described fragment that encompasses almost the entire extracellular domain of betaglycan (sBG-120) [16].
  • However, modulation of integrin and PECAM-1 levels and stimulation of mRNA levels for TGF-beta 1 and its receptors R-I, R-II, and betaglycan occurred normally in the endoglin transfectants [17].
  • In cultured granulosa-luteal cells, FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA, as did the protein kinase A activator dibutyryl cAMP and the protein kinase C inhibitor staurosporine [4].

Physical interactions of TGFBR3

  • Betaglycan is a membrane-anchored proteoglycan that binds transforming growth factor-beta (TGF-beta) via its core protein [16].
  • On the other hand, we found that the recently described ability of the wild type betaglycan to bind inhibin A is a property of the core protein that resides in the uromodulin-related region [18].
  • Collectively, these data show that the inhibin isoforms have different affinities for the activin type II receptors but bind betaglycan with high affinity [19].
  • Betaglycan also enables inhibin to bind to and compete with BMPs for binding to the BMP-specific type II receptor BMPRII, which does not bind inhibin in the absence of betaglycan [20].

Regulatory relationships of TGFBR3


Other interactions of TGFBR3

  • Because the membrane and soluble forms of betaglycan have opposite effects regulating the availability of TGF-beta, it is important to characterize the shedding of betaglycan further [16].
  • Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively [23].
  • Unexpectedly, during the course of these experiments, we observed that MT2-MMP decreases the levels of MT1-MMP and betaglycan [16].
  • The 38-kDa TGF-beta binding component, an N-linked glycoprotein, exhibits a higher affinity for TGF-beta 2 than for -beta 1 that is strikingly similar to that of the type III/betaglycan receptor [24].
  • Together with betaglycan, CD105 is considered as a TGF-betaR accessory molecule (also called TGF-betaRIII), but its functions in the receptor-ligand interactions are still poorly understood [25].

Analytical, diagnostic and therapeutic context of TGFBR3


  1. Oncogenic Ki-ras confers a more aggressive colon cancer phenotype through modification of transforming growth factor-beta receptor III. Yan, Z., Deng, X., Friedman, E. J. Biol. Chem. (2001) [Pubmed]
  2. The type III TGF-beta receptor suppresses breast cancer progression. Dong, M., How, T., Kirkbride, K.C., Gordon, K.J., Lee, J.D., Hempel, N., Kelly, P., Moeller, B.J., Marks, J.R., Blobe, G.C. J. Clin. Invest. (2007) [Pubmed]
  3. Down-regulation of transforming growth factor beta receptors by androgen in ovarian cancer cells. Evangelou, A., Jindal, S.K., Brown, T.J., Letarte, M. Cancer Res. (2000) [Pubmed]
  4. Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells. Liu, J., Kuulasmaa, T., Kosma, V.M., Bützow, R., Vänttinen, T., Hydén-Granskog, C., Voutilainen, R. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  5. Betaglycan presents ligand to the TGF beta signaling receptor. López-Casillas, F., Wrana, J.L., Massagué, J. Cell (1993) [Pubmed]
  6. Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system. López-Casillas, F., Cheifetz, S., Doody, J., Andres, J.L., Lane, W.S., Massagué, J. Cell (1991) [Pubmed]
  7. Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Lewis, K.A., Gray, P.C., Blount, A.L., MacConell, L.A., Wiater, E., Bilezikjian, L.M., Vale, W. Nature (2000) [Pubmed]
  8. Central role of TGF-beta in the pathogenesis of diabetic nephropathy and macrovascular complications: a hypothesis. Yokoyama, H., Deckert, T. Diabet. Med. (1996) [Pubmed]
  9. Eleven single nucleotide polymorphisms and one triple nucleotide insertion of the human TGF-beta III receptor gene. Zippert, R., Bässler, A., Holmer, S.R., Hengstenberg, C., Schunkert, H. J. Hum. Genet. (2000) [Pubmed]
  10. Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites. López-Casillas, F., Payne, H.M., Andres, J.L., Massagué, J. J. Cell Biol. (1994) [Pubmed]
  11. Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. Cheifetz, S., Bellón, T., Calés, C., Vera, S., Bernabeu, C., Massagué, J., Letarte, M. J. Biol. Chem. (1992) [Pubmed]
  12. TGFBR3 loss and consequences in prostate cancer. Sharifi, N., Hurt, E.M., Kawasaki, B.T., Farrar, W.L. Prostate (2007) [Pubmed]
  13. Recombinant soluble betaglycan is a potent and isoform-selective transforming growth factor-beta neutralizing agent. Vilchis-Landeros, M.M., Montiel, J.L., Mendoza, V., Mendoza-Hernández, G., López-Casillas, F. Biochem. J. (2001) [Pubmed]
  14. Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta. Hildebrand, A., Romarís, M., Rasmussen, L.M., Heinegård, D., Twardzik, D.R., Border, W.A., Ruoslahti, E. Biochem. J. (1994) [Pubmed]
  15. Expression and function of TbetaRII-B, a variant of the type II TGF-beta receptor, in human chondrocytes. Parker, W.L., Finnson, K.W., Soe-Lin, H., Knaus, P., Philip, A. Osteoarthr. Cartil. (2007) [Pubmed]
  16. The shedding of betaglycan is regulated by pervanadate and mediated by membrane type matrix metalloprotease-1. Velasco-Loyden, G., Arribas, J., López-Casillas, F. J. Biol. Chem. (2004) [Pubmed]
  17. Endoglin modulates cellular responses to TGF-beta 1. Lastres, P., Letamendía, A., Zhang, H., Rius, C., Almendro, N., Raab, U., López, L.A., Langa, C., Fabra, A., Letarte, M., Bernabéu, C. J. Cell Biol. (1996) [Pubmed]
  18. Ligand binding and functional properties of betaglycan, a co-receptor of the transforming growth factor-beta superfamily. Specialized binding regions for transforming growth factor-beta and inhibin A. Esparza-Lopez, J., Montiel, J.L., Vilchis-Landeros, M.M., Okadome, T., Miyazono, K., López-Casillas, F. J. Biol. Chem. (2001) [Pubmed]
  19. Properties of inhibin binding to betaglycan, InhBP/p120 and the activin type II receptors. Chapman, S.C., Bernard, D.J., Jelen, J., Woodruff, T.K. Mol. Cell. Endocrinol. (2002) [Pubmed]
  20. Inhibin is an antagonist of bone morphogenetic protein signaling. Wiater, E., Vale, W. J. Biol. Chem. (2003) [Pubmed]
  21. Plasmin cleaves betaglycan and releases a 60 kDa transforming growth factor-beta complex from the cell surface. Lamarre, J., Vasudevan, J., Gonias, S.L. Biochem. J. (1994) [Pubmed]
  22. Transforming growth factor-beta-1 latency-associated peptide and soluble betaglycan prevent a glucose-induced increase in fibronectin production in cultured human mesangial cells. Nomura, K., Tada, H., Kuboki, K., Inokuchi, T. Nephron (2002) [Pubmed]
  23. Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively. Johnson, D.W., Qumsiyeh, M., Benkhalifa, M., Marchuk, D.A. Genomics (1995) [Pubmed]
  24. Characterization of transforming growth factor-beta (TGF-beta) receptors on BeWo choriocarcinoma cells including the identification of a novel 38-kDa TGF-beta binding glycoprotein. Mitchell, E.J., Lee, K., O'Connor-McCourt, M.D. Mol. Biol. Cell (1992) [Pubmed]
  25. CD105 (endoglin) expression on hematopoietic stem/progenitor cells. Pierelli, L., Bonanno, G., Rutella, S., Marone, M., Scambia, G., Leone, G. Leuk. Lymphoma (2001) [Pubmed]
  26. Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. Bandyopadhyay, A., López-Casillas, F., Malik, S.N., Montiel, J.L., Mendoza, V., Yang, J., Sun, L.Z. Cancer Res. (2002) [Pubmed]
  27. Identification of endoglin in rat hepatic stellate cells: new insights into transforming growth factor beta receptor signaling. Meurer, S.K., Tihaa, L., Lahme, B., Gressner, A.M., Weiskirchen, R. J. Biol. Chem. (2005) [Pubmed]
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