Our website is made possible by displaying online advertisements to our visitors.
Please consider supporting us by disabling your ad blocker.

Responsive image


Transforming growth factor beta

Computer graphic of TGF-beta. TGF-beta is a cytokine with three different isoforms, which regulates many cellular functions including cell proliferation, differentiation, adhesion and migration

Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three[1] different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages.

Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors. TGF-β receptors are composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade.[2] This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells.[2][3]

TGF-β is secreted by many cell types, including macrophages, in a latent form in which it is complexed with two other polypeptides, latent TGF-beta binding protein (LTBP) and latency-associated peptide (LAP). Serum proteinases such as plasmin catalyze the release of active TGF-β from the complex. This often occurs on the surface of macrophages where the latent TGF-β complex is bound to CD36 via its ligand, thrombospondin-1 (TSP-1). Inflammatory stimuli that activate macrophages enhance the release of active TGF-β by promoting the activation of plasmin. Macrophages can also endocytose IgG-bound latent TGF-β complexes that are secreted by plasma cells and then release active TGF-β into the extracellular fluid.[4] Among its key functions is regulation of inflammatory processes, particularly in the gut.[5] TGF-β also plays a crucial role in stem cell differentiation as well as T-cell regulation and differentiation.[6][7]

Because of its role in immune and stem cell regulation and differentiation, it is a highly researched cytokine in the fields of cancer, auto-immune diseases, and infectious disease.

The TGF-β superfamily includes endogenous growth inhibiting proteins; an increase in expression of TGF-β often correlates with the malignancy of many cancers and a defect in the cellular growth inhibition response to TGF-β. Its immunosuppressive functions then come to dominate, contributing to oncogenesis.[8] The dysregulation of its immunosuppressive functions is also implicated in the pathogenesis of autoimmune diseases, although their effect is mediated by the environment of other cytokines present.[5][9]

  1. ^ Meng, Xiao-ming; Nikolic-Paterson, David J.; Lan, Hui Yao (June 2016). "TGF-β: the master regulator of fibrosis". Nature Reviews Nephrology. 12 (6): 325–338. doi:10.1038/nrneph.2016.48. PMID 27108839. S2CID 25871413.
  2. ^ a b Massagué J (October 2012). "TGFβ signalling in context". Nature Reviews. Molecular Cell Biology. 13 (10): 616–30. doi:10.1038/nrm3434. PMC 4027049. PMID 22992590.
  3. ^ Nakao A, Afrakhte M, Morén A, Nakayama T, Christian JL, Heuchel R, et al. (October 1997). "Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling". Nature. 389 (6651): 631–5. Bibcode:1997Natur.389..631N. doi:10.1038/39369. PMID 9335507. S2CID 4311145.
  4. ^ AfCS signaling gateway – data center – ligand description
  5. ^ a b Letterio JJ, Roberts AB (April 1998). "Regulation of immune responses by TGF-beta". Annual Review of Immunology. 16 (1): 137–61. doi:10.1146/annurev.immunol.16.1.137. PMID 9597127.
  6. ^ Massagué J, Xi Q (July 2012). "TGF-β control of stem cell differentiation genes". FEBS Letters. 586 (14): 1953–8. doi:10.1016/j.febslet.2012.03.023. PMC 3466472. PMID 22710171.
  7. ^ Li MO, Flavell RA (August 2008). "TGF-beta: a master of all T cell trades". Cell. 134 (3): 392–404. doi:10.1016/j.cell.2008.07.025. PMC 3677783. PMID 18692464.
  8. ^ Massagué J, Blain SW, Lo RS (October 2000). "TGFbeta signaling in growth control, cancer, and heritable disorders". Cell. 103 (2): 295–309. doi:10.1016/S0092-8674(00)00121-5. PMID 11057902. S2CID 15482063.
  9. ^ Lichtman, Michael K.; Otero-Vinas, Marta; Falanga, Vincent (March 2016). "Transforming growth factor beta (TGF-β) isoforms in wound healing and fibrosis". Wound Repair and Regeneration. 24 (2): 215–222. doi:10.1111/wrr.12398. ISSN 1524-475X. PMID 26704519. S2CID 4967954.

Previous Page Next Page