TGFBR3
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| Location (UCSC) | Chr 1: 91.68 – 91.91 Mb | Chr 5: 107.25 – 107.44 Mb | |||||||
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Betaglycan also known as Transforming growth factor beta receptor III (TGFBR3), is a cell-surface
Study of a mouse knock-out for the Tgfbr3 gene showed a fundamental effect on the correct development of organs and the overall viability of the animals used. Within the same study, no significant changes in Smad signalling (typical for TGF-beta cascade) were detected. This fact suggests that additional, as yet undescribed functions of betaglycan may be mediated by non-classical signalling pathways.[7]
Domains and function
TGFBR3 is composed of an extracellular receptor domain consisting of 849 amino acids which is intracellularly connected to a short cytoplasmic domain. Betaglycan, being expressed by a whole range of various cell types within the organism, can be found in the form of a membrane-bound receptor, or as a soluble protein capable of interactions with the extracellular matrix (ECM).[7][9]
The formation of soluble betaglycan is mediated by metalloproteinases and other enzymes present in the ECM.[9] Proteolytic cleavage releases an ectodomain containing two binding sites for TGF-beta. Due to high affinity to its ligand, free betaglycan is an important factor in the deposition and neutralization of this cytokine within the ECM. The ratio of membrane and soluble variant in the organism significantly affects the availability of TGF-beta and subsequent intracellular signalling.[10]
The cytoplasmic domain mediates interactions with scaffold proteins inside the cell. These intracellular interactions do not affect the functionality of the ectodomain - nor its affinity to TGF-beta. However, they affect cell migration and the overall responsiveness of a given cell to the action of TGF-beta.[7][11]
Re-release of the cytokine can occur due to the proteolytic activity of the pro-apoptotic serine protease - granzyme B.[12] Plasmin - a serine protease present in the blood, activated as part of inflammatory reactions, then participates in the definitive degradation of betaglycan.[10]
See also
- TGF beta receptors
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000069702 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029287 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 2592419.
- ^ PMID 1556106.
- ^ S2CID 52164499.
- PMID 30995507.
- ^ PMID 14672946.
- ^ PMID 19842711.
- S2CID 198172452.
- PMID 22479366.
Further reading
- Massagué J (1992). "Receptors for the TGF-beta family". Cell. 69 (7): 1067–70. S2CID 54268875.
- Border WA, Noble NA (1994). "Transforming growth factor beta in tissue fibrosis". N. Engl. J. Med. 331 (19): 1286–92. PMID 7935686.
- Morén A, Ichijo H, Miyazono K (1992). "Molecular cloning and characterization of the human and porcine transforming growth factor-beta type III receptors". Biochem. Biophys. Res. Commun. 189 (1): 356–62. PMID 1333192.
- López-Casillas F, Cheifetz S, Doody J, et al. (1991). "Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system". Cell. 67 (4): 785–95. S2CID 54304782.
- Wang XF, Lin HY, Ng-Eaton E, et al. (1991). "Expression cloning and characterization of the TGF-beta type III receptor". Cell. 67 (4): 797–805. S2CID 54258148.
- Lin HY, Moustakas A, Knaus P, et al. (1995). "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. 270 (6): 2747–54. PMID 7852346.
- López-Casillas F, Payne HM, Andres JL, Massagué J (1994). "Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites". J. Cell Biol. 124 (4): 557–68. PMID 8106553.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Johnson DW, Qumsiyeh M, Benkhalifa M, Marchuk DA (1996). "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. 28 (2): 356–7. PMID 8530052.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. PMID 9373149.
- Brown CB, Boyer AS, Runyan RB, Barnett JV (1999). "Requirement of type III TGF-beta receptor for endocardial cell transformation in the heart". Science. 283 (5410): 2080–2. PMID 10092230.
- Gao J, Symons AL, Bartold PM (1999). "Expression of transforming growth factor-beta receptors types II and III within various cells in the rat periodontium". Journal of Periodontal Research. 34 (2): 113–22. PMID 10207840.
- Lewis KA, Gray PC, Blount AL, et al. (2000). "Betaglycan binds inhibin and can mediate functional antagonism of activin signalling". Nature. 404 (6776): 411–4. S2CID 4393629.
- Zippert R, Bässler A, Holmer SR, et al. (2000). "Eleven single nucleotide polymorphisms and one triple nucleotide insertion of the human TGF-beta III receptor gene". J. Hum. Genet. 45 (4): 250–3. PMID 10944857.
- Rotzer D, Roth M, Lutz M, et al. (2001). "Type III TGF-β receptor-independent signalling of TGF-β2 via TβRII-B, an alternatively spliced TGF-β type II receptor". EMBO J. 20 (3): 480–90. PMID 11157754.
- Blobe GC, Schiemann WP, Pepin MC, et al. (2001). "Functional roles for the cytoplasmic domain of the type III transforming growth factor beta receptor in regulating transforming growth factor beta signaling". J. Biol. Chem. 276 (27): 24627–37. PMID 11323414.
- De Crescenzo G, Grothe S, Zwaagstra J, et al. (2001). "Real-time monitoring of the interactions of transforming growth factor-beta (TGF-beta ) isoforms with latency-associated protein and the ectodomains of the TGF-beta type II and III receptors reveals different kinetic models and stoichiometries of binding". J. Biol. Chem. 276 (32): 29632–43. PMID 11382746.
- Blobe GC, Liu X, Fang SJ, et al. (2001). "A novel mechanism for regulating transforming growth factor beta (TGF-beta) signaling. Functional modulation of type III TGF-beta receptor expression through interaction with the PDZ domain protein, GIPC". J. Biol. Chem. 276 (43): 39608–17. PMID 11546783.
External links
- betaglycan at the U.S. National Library of Medicine Medical Subject Headings (MeSH)