TGFBR3

Last updated
TGFBR3
Identifiers
Aliases TGFBR3 , BGCAN, betaglycan, transforming growth factor beta receptor 3
External IDs OMIM: 600742 MGI: 104637 HomoloGene: 2436 GeneCards: TGFBR3
Orthologs
SpeciesHumanMouse
Entrez

7049

21814

Ensembl

ENSG00000069702

ENSMUSG00000029287

UniProt

Q03167

O88393

RefSeq (mRNA)

NM_001195683
NM_001195684
NM_003243

NM_011578

RefSeq (protein)

NP_001182612
NP_001182613
NP_003234

NP_035708

Location (UCSC) Chr 1: 91.68 – 91.91 Mb Chr 5: 107.25 – 107.44 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Betaglycan also known as Transforming growth factor beta receptor III (TGFBR3), is a cell-surface chondroitin sulfate / heparan sulfate proteoglycan >300 kDa in molecular weight. Betaglycan binds to various members of the TGF-beta superfamily of ligands via its core protein, and bFGF via its heparan sulfate chains. [5] [6] TGFBR3 is the most widely expressed type of TGF-beta receptor. Its affinity towards all individual isoforms of TGF-beta is similarly high and therefore it plays an important role as a coreceptor mediating the binding of TGF-beta to its other receptors - specifically TGFBR2. The intrinsic kinase activity of this receptor has not yet been described. In regard of TGF-beta signalling it is generally considered a non-signaling receptor or a coreceptor. [7] [8] By binding to various member of the TGF-beta superfamily at the cell surface it acts as a reservoir of TGF-beta. [6]

Contents

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

Related Research Articles

<span class="mw-page-title-main">Transforming growth factor beta</span> Cytokine

Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages.

<span class="mw-page-title-main">Decorin</span> Protein-coding gene in humans

Decorin is a protein that in humans is encoded by the DCN gene.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 2</span> Protein-coding gene in the species Homo sapiens

Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the SMAD2 gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 3</span> Protein-coding gene in humans

Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 7</span> Protein-coding gene in the species Homo sapiens

Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene.

Smads comprise a family of structurally similar proteins that are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily, which are critically important for regulating cell development and growth. The abbreviation refers to the homologies to the Caenorhabditis elegans SMA and MAD family of genes in Drosophila.

The transforming growth factor beta (TGFB) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, cell migration, apoptosis, cellular homeostasis and other cellular functions. The TGFB signaling pathways are conserved. In spite of the wide range of cellular processes that the TGFβ signaling pathway regulates, the process is relatively simple. TGFβ superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor. The type I receptor then phosphorylates receptor-regulated SMADs (R-SMADs) which can now bind the coSMAD SMAD4. R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression.

<span class="mw-page-title-main">TGF beta 1</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation, and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene.

<span class="mw-page-title-main">ACVR1B</span> Protein-coding gene in humans

Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.

<span class="mw-page-title-main">ACVR2A</span> Protein-coding gene in the species Homo sapiens

Activin receptor type-2A is a protein that in humans is encoded by the ACVR2A gene. ACVR2A is an activin type 2 receptor.

<span class="mw-page-title-main">Endoglin</span> Protein-coding gene in the species Homo sapiens

Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefore, making it an important protein for tumor growth, survival and metastasis of cancer cells to other locations in the body.

<span class="mw-page-title-main">CTGF</span> Protein-coding gene in the species Homo sapiens

CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins. CTGF has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancers.

Transforming growth factor beta (TGFβ) receptors are single pass serine/threonine kinase receptors that belong to TGFβ receptor family. They exist in several different isoforms that can be homo- or heterodimeric. The number of characterized ligands in the TGFβ superfamily far exceeds the number of known receptors, suggesting the promiscuity that exists between the ligand and receptor interactions.

<span class="mw-page-title-main">TGF beta 2</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor-beta 2 (TGF-β2) is a secreted protein known as a cytokine that performs many cellular functions and has a vital role during embryonic development. It is an extracellular glycosylated protein. It is known to suppress the effects of interleukin dependent T-cell tumors. There are two named isoforms of this protein, created by alternative splicing of the same gene.

<span class="mw-page-title-main">TGF beta receptor 1</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta receptor I is a membrane-bound TGF beta receptor protein of the TGF-beta receptor family for the TGF beta superfamily of signaling ligands. TGFBR1 is its human gene.

<span class="mw-page-title-main">Transforming growth factor, beta 3</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta-3 is a protein that in humans is encoded by the TGFB3 gene.

<span class="mw-page-title-main">LTBP1 (gene)</span> Protein-coding gene in the species Homo sapiens

Latent-transforming growth factor beta-binding protein 1 is a protein that in humans is encoded by the LTBP1 gene.

<span class="mw-page-title-main">LTBP3</span> Protein-coding gene in the species Homo sapiens

Latent-transforming growth factor beta-binding protein 3 is a protein that in humans is encoded by the LTBP3 gene.

Transforming growth factor beta (TGF-β) is a potent cell regulatory polypeptide homodimer of 25kD. It is a multifunctional signaling molecule with more than 40 related family members. TGF-β plays a role in a wide array of cellular processes including early embryonic development, cell growth, differentiation, motility, and apoptosis.

The transforming growth factor beta (TGFβ) receptors are a family of serine/threonine kinase receptors involved in TGF beta signaling pathway. These receptors bind growth factor and cytokine signaling proteins in the TGF-beta family such as TGFβs, bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), activin and inhibin, myostatin, anti-Müllerian hormone (AMH), and NODAL.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000069702 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029287 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Andres JL, Stanley K, et al. (1989). "Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta". J. Cell Biol. 109 (6 (Pt 1)): 3137–3145. doi:10.1083/jcb.109.6.3137. PMC   2115961 . PMID   2592419.
  6. 1 2 Andres JL, DeFalcis D, et al. (1992). "Binding of two growth factor families to separate domains of the proteoglycan betaglycan". J. Biol. Chem. 267 (9): 5927–5930. doi: 10.1016/S0021-9258(18)42643-9 . PMID   1556106.
  7. 1 2 3 4 Vander Ark, Alexandra; Cao, Jingchen; Li, Xiaohong (2018-12-01). "TGF-β receptors: In and beyond TGF-β signaling". Cellular Signalling. 52: 112–120. doi: 10.1016/j.cellsig.2018.09.002 . ISSN   0898-6568. PMID   30184463. S2CID   52164499.
  8. ↑ Batlle, Eduard; Massagué, Joan (April 2019). "Transforming Growth Factor-β Signaling in Immunity and Cancer". Immunity. 50 (4): 924–940. doi:10.1016/j.immuni.2019.03.024. ISSN   1074-7613. PMC   7507121 . PMID   30995507.
  9. 1 2 Velasco-Loyden, Gabriela; Arribas, Joaquín; López-Casillas, Fernando (February 2004). "The Shedding of Betaglycan Is Regulated by Pervanadate and Mediated by Membrane Type Matrix Metalloprotease-1". Journal of Biological Chemistry. 279 (9): 7721–7733. doi: 10.1074/jbc.m306499200 . ISSN   0021-9258. PMID   14672946.
  10. 1 2 Mendoza, Valentín; Vilchis-Landeros, M. Magdalena; Mendoza-Hernández, Guillermo; Huang, Tao; Villarreal, Maria M.; Hinck, Andrew P.; López-Casillas, Fernando; Montiel, Jose-Luis (2009-12-15). "Betaglycan has Two Independent Domains Required for High Affinity TGF-β Binding: Proteolytic Cleavage Separates the Domains and Inactivates the Neutralizing Activity of the Soluble Receptor". Biochemistry. 48 (49): 11755–11765. doi:10.1021/bi901528w. ISSN   0006-2960. PMC   2796082 . PMID   19842711.
  11. ↑ Chen, Yuhong; Di, Cuixia; Zhang, Xuetian; Wang, Jing; Wang, Fang; Yan, Jun‐fang; Xu, Caipeng; Zhang, Jinhua; Zhang, Qianjing; Li, Hongyan; Yang, Hongying (March 2020). "Transforming growth factor β signaling pathway: A promising therapeutic target for cancer". Journal of Cellular Physiology. 235 (3): 1903–1914. doi:10.1002/jcp.29108. ISSN   0021-9541. PMID   31332789. S2CID   198172452.
  12. ↑ Boivin, Wendy A.; Shackleford, Marlo; Hoek, Amanda Vanden; Zhao, Hongyan; Hackett, Tillie L.; Knight, Darryl A.; Granville, David J. (2012-03-30). "Granzyme B Cleaves Decorin, Biglycan and Soluble Betaglycan, Releasing Active Transforming Growth Factor-β1". PLOS ONE. 7 (3): e33163. Bibcode:2012PLoSO...733163B. doi: 10.1371/journal.pone.0033163 . ISSN   1932-6203. PMC   3316562 . PMID   22479366.

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