Biology:TGF beta 1

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Short description: Protein-coding gene in the species Homo sapiens


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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.[1][2]

Function

TGF-β is a multifunctional set of peptides that controls proliferation, differentiation, and other functions in many cell types. TGF-β acts synergistically with transforming growth factor-alpha (TGF-α) in inducing transformation. It also acts as a negative autocrine growth factor. Dysregulation of TGF-β activation and signaling may result in apoptosis. Many cells synthesize TGF-β and almost all of them have specific receptors for this peptide. TGF-β1, TGF-β2, and TGF-β3 all function through the same receptor signaling systems.[3]

TGF-β1 was first identified in human platelets as a protein with a molecular mass of 25 kilodaltons with a potential role in wound healing.[4][5] It was later characterized as a large protein precursor (containing 390 amino acids) that was proteolytically processed to produce a mature peptide of 112 amino acids.[6]

TGF-β1 plays an important role in controlling the immune system, and shows different activities on different types of cell, or cells at different developmental stages. Most immune cells (or leukocytes) secrete TGF-β1.[7]

T cells

Some T cells (e.g. regulatory T cells) release TGF-β1 to inhibit the actions of other T cells. Specifically, TGF-β1 prevents the interleukin(IL)-1- & interleukin-2-dependent proliferation in activated T cells,[8][9] as well as the activation of quiescent helper T cells and cytotoxic T cells.[10][11] Similarly, TGF-β1 can inhibit the secretion and activity of many other cytokines including interferon-γ, tumor necrosis factor-alpha (TNF-α), and various interleukins. It can also decrease the expression levels of cytokine receptors, such as the IL-2 receptor to down-regulate the activity of immune cells. However, TGF-β1 can also increase the expression of certain cytokines in T cells and promote their proliferation,[12] particularly if the cells are immature.[7]

B cells

TGF-β1 has similar effects on B cells that also vary according to the differentiation state of the cell. It inhibits proliferation, stimulates apoptosis of B cells,[13] and controls the expression of antibody, transferrin and MHC class II proteins on immature and mature B cells.[7][13]

Myeloid cells

The effects of TGF-β1 on macrophages and monocytes are predominantly suppressive; this cytokine can inhibit the proliferation of these cells and prevent their production of reactive oxygen (e.g. superoxide (O2−)) and nitrogen (e.g. nitric oxide (NO)) intermediates. However, as with other cell types, TGF-β1 can also have the opposite effect on cells of myeloid origin. For example, TGF-β1 acts as a chemoattractant, directing an immune response to certain pathogens. Likewise, macrophages and monocytes respond to low levels of TGF-β1 in a chemotactic manner. Furthermore, the expression of monocytic cytokines (such as interleukin(IL)-1α, IL-1β, and TNF-α),[11] and macrophage's phagocytic can be increased by the action of TGF-β1.[7]

TGF-β1 reduces the efficacy of the MHC II in astrocytes and dendritic cells, which in turn decreases the activation of appropriate helper T cell populations.[14][15]

Interactions

TGF beta 1 has been shown to interact with:

References

  1. ↑ "Genetic mapping of the Camurati-Engelmann disease locus to chromosome 19q13.1-q13.3". Am. J. Hum. Genet. 66 (1): 143–7. January 2000. doi:10.1086/302728. PMID 10631145. 
  2. ↑ "Confirmation of the mapping of the Camurati-Englemann locus to 19q13. 2 and refinement to a 3.2-cM region". Genomics 66 (1): 119–21. May 2000. doi:10.1006/geno.2000.6192. PMID 10843814. 
  3. ↑ "Entrez Gene: TGFB1 transforming growth factor, beta 1". https://www.ncbi.nlm.nih.gov/gene/7040. 
  4. ↑ "Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization". J. Biol. Chem. 258 (11): 7155–60. 1983. doi:10.1016/S0021-9258(18)32345-7. PMID 6602130. 
  5. ↑ Custo, S; Baron, B; Felice, A; Seria, E (5 July 2022). "A comparative profile of total protein and six angiogenically-active growth factors in three platelet products". GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW 11 (Doc06): Doc06. doi:10.3205/iprs000167. PMID 35909816. PMC 9284722. https://www.egms.de/static/en/journals/iprs/2022-11/iprs000167.shtml#block5. 
  6. ↑ "Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells". Nature 316 (6030): 701–5. 1985. doi:10.1038/316701a0. PMID 3861940. Bibcode: 1985Natur.316..701D. https://zenodo.org/record/1233037. 
  7. ↑ 7.0 7.1 7.2 7.3 "Regulation of immune responses by TGF-beta". Annu. Rev. Immunol. 16: 137–61. 1998. doi:10.1146/annurev.immunol.16.1.137. PMID 9597127. https://zenodo.org/record/1234983. 
  8. ↑ "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J. Immunol. 140 (9): 3026–32. 1988. doi:10.4049/jimmunol.140.9.3026. PMID 3129508. 
  9. ↑ "Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response". Int. Immunol. 15 (12): 1495–504. 2003. doi:10.1093/intimm/dxg147. PMID 14645158. 
  10. ↑ "Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in naive T cells". Immunol. Invest. 26 (4): 459–72. 1997. doi:10.3109/08820139709022702. PMID 9246566. 
  11. ↑ 11.0 11.1 "TGF-beta: a mobile purveyor of immune privilege". Immunol. Rev. 213: 213–27. 2006. doi:10.1111/j.1600-065X.2006.00437.x. PMID 16972906. https://zenodo.org/record/1230716. 
  12. ↑ "Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage". Prog. Neurobiol. 178: 101610. March 2019. doi:10.1016/j.pneurobio.2019.03.003. PMID 30923023. 
  13. ↑ 13.0 13.1 "The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes". Microbes Infect. 1 (15): 1297–304. 1999. doi:10.1016/S1286-4579(99)00254-3. PMID 10611758. 
  14. ↑ "Human myeloid dendritic cells treated with supernatants of rotavirus infected Caco-2 cells induce a poor Th1 response". Cellular Immunology 272 (2): 154–61. 2012-01-01. doi:10.1016/j.cellimm.2011.10.017. PMID 22082567. 
  15. ↑ "The Smad3 protein is involved in TGF-beta inhibition of class II transactivator and class II MHC expression". Journal of Immunology 167 (1): 311–9. July 2001. doi:10.4049/jimmunol.167.1.311. PMID 11418665. 
  16. ↑ "Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta". Biochem. J. 302 (2): 527–34. September 1994. doi:10.1042/bj3020527. PMID 8093006. 
  17. ↑ "Decorin core protein fragment Leu155-Val260 interacts with TGF-beta but does not compete for decorin binding to type I collagen". Arch. Biochem. Biophys. 355 (2): 241–8. July 1998. doi:10.1006/abbi.1998.0720. PMID 9675033. 
  18. ↑ "Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity". J. Biol. Chem. 269 (51): 32634–8. Dec 1994. doi:10.1016/S0021-9258(18)31681-8. PMID 7798269. 
  19. ↑ "The type II transforming growth factor (TGF)-beta receptor-interacting protein TRIP-1 acts as a modulator of the TGF-beta response". J. Biol. Chem. 273 (47): 31455–62. November 1998. doi:10.1074/jbc.273.47.31455. PMID 9813058. 
  20. ↑ "Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta". Mol. Biol. Cell 11 (8): 2691–704. August 2000. doi:10.1091/mbc.11.8.2691. PMID 10930463. 
  21. ↑ "Determination of type I receptor specificity by the type II receptors for TGF-beta or activin". Science 262 (5135): 900–2. November 1993. doi:10.1126/science.8235612. PMID 8235612. Bibcode: 1993Sci...262..900E. 
  22. ↑ "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc. Natl. Acad. Sci. U.S.A. 97 (6): 2626–31. March 2000. doi:10.1073/pnas.97.6.2626. PMID 10716993. Bibcode: 2000PNAS...97.2626O. 
  23. ↑ "Conserved role for 14-3-3epsilon downstream of type I TGFbeta receptors". FEBS Lett. 490 (1–2): 65–9. February 2001. doi:10.1016/s0014-5793(01)02133-0. PMID 11172812. 

Further reading

External links

  • Overview of all the structural information available in the PDB for UniProt: P01137 (Transforming growth factor beta-1) at the PDBe-KB.




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