TGF beta 1: Wikis

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Transforming growth factor, beta 1

PDB rendering based on 1kla.
Available structures
1kla, 1klc, 1kld
Identifiers
Symbols TGFB1; CED; DPD1; TGFB
External IDs OMIM190180 MGI98725 HomoloGene540 GeneCards: TGFB1 Gene
RNA expression pattern
PBB GE TGFB1 203085 s at.png
PBB GE TGFB1 203084 at.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7040 21803
Ensembl ENSG00000105329 ENSMUSG00000002603
UniProt P01137 Q3UNK5
RefSeq (mRNA) NM_000660 NM_011577
RefSeq (protein) NP_000651 NP_035707
Location (UCSC) Chr 19:
46.53 - 46.55 Mb
Chr 7:
25.4 - 25.41 Mb
PubMed search [1] [2]

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]

Contents

Function

TGFB is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types. TGFB acts synergistically with TGFA in inducing transformation. It also acts as a negative autocrine growth factor. Dysregulation of TGFB activation and signaling may result in apoptosis. Many cells synthesize TGFB and almost all of them have specific receptors for this peptide. TGFB1, TGFB2, and TGFB3 all function through the same receptor signaling systems.[supplied by OMIM][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] 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.[5]

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.[6]

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TGF-β1 and T cells

Some T cells (e.g. regulatory T cells) release TGF-β1 to inhibit the actions of other T cells. Interleukin 1- and interleukin 2-dependent proliferation of activated T cells,[7][8] and the activation of quiescent helper T cells and cytotoxic T cells is prevented by the activity of TGF-β1.[9][10] 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, particularly if the cells are immature.[11]

TGF-β1 and B cells

TGF-β1 has similar effects on B cells that also vary according to the differentiation state of the cell. It inhibits proliferation and apoptosis of B cells,[12] and plays a role in controlling the expression of antibody, transferrin and MHC class II proteins on immature and mature B cells.[6][12]

TGF-β1 and myeloid cells

The effects of TGF-β1 on macrophages and monocytes is 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 some pathogens; macrophages and monocytes respond to low levels of TGF-β1 in a chemotactic manner. Furthermore, the expression of monocytic cytokines (including interleukin-1(IL-1)-alpha, IL-1-beta, and TNF-α), [10] and phagocytic killing by macrophages can be increased by the action of TGF-β1.[6]

Interactions

TGF beta 1 has been shown to interact with TGF beta receptor 1,[13][14] LTBP1,[15] YWHAE,[16] EIF3I[17] and Decorin.[18][19][20]

References

  1. ^ Ghadami M, Makita Y, Yoshida K, Nishimura G, Fukushima Y, Wakui K, Ikegawa S, Yamada K, Kondo S, Niikawa N, Tomita H (January 2000). "Genetic mapping of the Camurati-Engelmann disease locus to chromosome 19q13.1-q13.3". Am. J. Hum. Genet. 66 (1): 143–7. doi:10.1086/302728. PMID 10631145.  
  2. ^ Vaughn SP, Broussard S, Hall CR, Scott A, Blanton SH, Milunsky JM, Hecht JT (May 2000). "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. doi:10.1006/geno.2000.6192. PMID 10843814.  
  3. ^ "Entrez Gene: TGFB1 transforming growth factor, beta 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7040.  
  4. ^ Assoian R, Komoriya A, Meyers C, Miller D, Sporn M (1983). "Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization". J Biol Chem 258 (11): 7155–60. PMID 6602130.  
  5. ^ Derynck R, Jarrett J, Chen E, Eaton D, Bell J, Assoian R, Roberts A, Sporn M, Goeddel D (1985). "Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells". Nature 316 (6030): 701–5. doi:10.1038/316701a0. PMID 3861940.  
  6. ^ a b c Letterio J, Roberts A (1998). "Regulation of immune responses by TGF-beta". Annu Rev Immunol 16: 137–61. doi:10.1146/annurev.immunol.16.1.137. PMID 9597127.  
  7. ^ Wahl S, Hunt D, Wong H, Dougherty S, McCartney-Francis N, Wahl L, Ellingsworth L, Schmidt J, Hall G, Roberts A (1988). "Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation". J Immunol 140 (9): 3026–32. PMID 3129508.  
  8. ^ Tiemessen M, Kunzmann S, Schmidt-Weber C, Garssen J, Bruijnzeel-Koomen C, Knol E, van Hoffen E (2003). "Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response". Int Immunol 15 (12): 1495–504. doi:10.1093/intimm/dxg147. PMID 14645158.  
  9. ^ Gilbert K, Thoman M, Bauche K, Pham T, Weigle W (1997). "Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in naive T cells". Immunol Invest 26 (4): 459–72. doi:10.3109/08820139709022702. PMID 9246566.  
  10. ^ a b Wahl S, Wen J, Moutsopoulos N (2006). "TGF-beta: a mobile purveyor of immune privilege". Immunol Rev 213: 213–27. doi:10.1111/j.1600-065X.2006.00437.x. PMID 16972906.  
  11. ^ Letterio J, Roberts A (1998). "Regulation of immune responses by TGF-beta". Annu Rev Immunol 16: 137–61. doi:10.1146/annurev.immunol.16.1.137. PMID 9597127.  
  12. ^ a b Lebman D, Edmiston J (1999). "The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes". Microbes Infect 1 (15): 1297–304. doi:10.1016/S1286-4579(99)00254-3. PMID 10611758.  
  13. ^ Ebner, R; Chen R H, Lawler S, Zioncheck T, Derynck R (Nov. 1993). "Determination of type I receptor specificity by the type II receptors for TGF-beta or activin". Science (UNITED STATES) 262 (5135): 900–2. ISSN 0036-8075. PMID 8235612.  
  14. ^ Oh, S P; Seki T, Goss K A, Imamura T, Yi Y, Donahoe P K, Li L, Miyazono K, ten Dijke P, Kim S, Li E (Mar. 2000). "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (6): 2626–31. ISSN 0027-8424. PMID 10716993.  
  15. ^ Saharinen, J; Keski-Oja J (Aug. 2000). "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 (UNITED STATES) 11 (8): 2691–704. ISSN 1059-1524. PMID 10930463.  
  16. ^ McGonigle, S; Beall M J, Feeney E L, Pearce E J (Feb. 2001). "Conserved role for 14-3-3epsilon downstream of type I TGFbeta receptors". FEBS Lett. (Netherlands) 490 (1-2): 65–9. ISSN 0014-5793. PMID 11172812.  
  17. ^ Choy, L; Derynck R (Nov. 1998). "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. (UNITED STATES) 273 (47): 31455–62. ISSN 0021-9258. PMID 9813058.  
  18. ^ Hildebrand, A; Romarís M, Rasmussen L M, Heinegård D, Twardzik D R, Border W A, Ruoslahti E (Sep. 1994). "Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta". Biochem. J. (ENGLAND) 302 ( Pt 2): 527–34. ISSN 0264-6021. PMID 8093006.  
  19. ^ Schönherr, E; Broszat M, Brandan E, Bruckner P, Kresse H (Jul. 1998). "Decorin core protein fragment Leu155-Val260 interacts with TGF-beta but does not compete for decorin binding to type I collagen". Arch. Biochem. Biophys. (UNITED STATES) 355 (2): 241–8. doi:10.1006/abbi.1998.0720. ISSN 0003-9861. PMID 9675033.  
  20. ^ Takeuchi, Y; Kodama Y, Matsumoto T (Dec. 1994). "Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity". J. Biol. Chem. (UNITED STATES) 269 (51): 32634–8. ISSN 0021-9258. PMID 7798269.  

Further reading

  • Border WA, Noble NA (1994). "Transforming growth factor beta in tissue fibrosis.". N. Engl. J. Med. 331 (19): 1286–92. doi:10.1056/NEJM199411103311907. PMID 7935686.  
  • Munger JS, Harpel JG, Gleizes PE, et al. (1997). "Latent transforming growth factor-beta: structural features and mechanisms of activation.". Kidney Int. 51 (5): 1376–82. doi:10.1038/ki.1997.188. PMID 9150447.  
  • Iozzo RV (1999). "The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins.". J. Biol. Chem. 274 (27): 18843–6. doi:10.1074/jbc.274.27.18843. PMID 10383378.  
  • Reinhold D, Wrenger S, Kähne T, Ansorge S (1999). "HIV-1 Tat: immunosuppression via TGF-beta1 induction.". Immunol. Today 20 (8): 384–5. doi:10.1016/S0167-5699(99)01497-8. PMID 10431160.  
  • Yamada Y (2002). "Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis.". Pharmacogenetics 11 (9): 765–71. doi:10.1097/00008571-200112000-00004. PMID 11740340.  
  • Chen W, Wahl SM (2002). "TGF-beta: receptors, signaling pathways and autoimmunity.". Curr. Dir. Autoimmun. 5: 62–91. doi:10.1159/000060548. PMID 11826761.  
  • Marone M, Bonanno G, Rutella S, et al. (2003). "Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21.". Leuk. Lymphoma 43 (1): 51–7. doi:10.1080/10428190210195. PMID 11908736.  
  • Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC (2003). "TGF-beta signal transduction and mesangial cell fibrogenesis.". Am. J. Physiol. Renal Physiol. 284 (2): F243–52. doi:10.1152/ajprenal.00300.2002. PMID 12529270.  
  • Kalluri R, Neilson EG (2004). "Epithelial-mesenchymal transition and its implications for fibrosis.". J. Clin. Invest. 112 (12): 1776–84. doi:10.1172/JCI200320530. PMID 14679171.  
  • Grainger DJ (2005). "Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis.". Arterioscler. Thromb. Vasc. Biol. 24 (3): 399–404. doi:10.1161/01.ATV.0000114567.76772.33. PMID 14699019.  
  • Attisano L, Labbé E (2004). "TGFbeta and Wnt pathway cross-talk.". Cancer Metastasis Rev. 23 (1-2): 53–61. doi:10.1023/A:1025811012690. PMID 15000149.  
  • McGowan TA, Zhu Y, Sharma K (2005). "Transforming growth factor-beta: a clinical target for the treatment of diabetic nephropathy.". Curr. Diab. Rep. 4 (6): 447–54. doi:10.1007/s11892-004-0055-z. PMID 15539010.  
  • Sheppard D (2006). "Integrin-mediated activation of latent transforming growth factor beta.". Cancer Metastasis Rev. 24 (3): 395–402. doi:10.1007/s10555-005-5131-6. PMID 16258727.  
  • Gressner AM, Weiskirchen R (2006). "Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets.". J. Cell. Mol. Med. 10 (1): 76–99. doi:10.1111/j.1582-4934.2006.tb00292.x. PMID 16563223.  
  • Seoane J (2006). "Escaping from the TGFbeta anti-proliferative control.". Carcinogenesis 27 (11): 2148–56. doi:10.1093/carcin/bgl068. PMID 16698802.  
  • Lee CG, Kang HR, Homer RJ, et al. (2006). "Transgenic modeling of transforming growth factor-beta(1): role of apoptosis in fibrosis and alveolar remodeling.". Proceedings of the American Thoracic Society 3 (5): 418–23. doi:10.1513/pats.200602-017AW. PMID 16799085.  
  • Wahl SM (2007). "Transforming growth factor-beta: innately bipolar.". Curr. Opin. Immunol. 19 (1): 55–62. doi:10.1016/j.coi.2006.11.008. PMID 17137775.  
  • Redondo S, Santos-Gallego CG, Tejerina T (2007). "TGF-beta1: a novel target for cardiovascular pharmacology.". Cytokine Growth Factor Rev. 18 (3-4): 279–86. doi:10.1016/j.cytogfr.2007.04.005. PMID 17485238.  

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