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{{Protbox
{{Infobox_gene}}
  |Name=Transforming growth factor beta-1
'''Transforming growth factor beta 1''' or '''TGF-β1''' is a polypeptide member of the [[transforming growth factor beta superfamily]] of [[cytokine]]s. 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]].<ref name="pmid10631145">{{cite journal | vauthors = Ghadami M, Makita Y, Yoshida K, Nishimura G, Fukushima Y, Wakui K, Ikegawa S, Yamada K, Kondo S, Niikawa N, ((Tomita Ha)) | title = Genetic mapping of the Camurati-Engelmann disease locus to chromosome 19q13.1-q13.3 | journal = Am. J. Hum. Genet. | volume = 66 | issue = 1 | pages = 143–7  | date = January 2000 | pmid = 10631145 | pmc = 1288319 | doi = 10.1086/302728 }}</ref><ref name="pmid10843814">{{cite journal | vauthors = Vaughn SP, Broussard S, Hall CR, Scott A, Blanton SH, Milunsky JM, Hecht JT | title = Confirmation of the mapping of the Camurati-Englemann locus to 19q13. 2 and refinement to a 3.2-cM region | journal = Genomics | volume = 66 | issue = 1 | pages = 119–21  | date = May 2000 | pmid = 10843814 | doi = 10.1006/geno.2000.6192 }}</ref>
  |Photo=TGFbeta1.png
|width=240px
  |Caption='''Solution Structure Of TGF-β1'''
  |Gene = [[HUGO]] code:[http://www.gene.ucl.ac.uk/nomenclature/data/get_data.php?hgnc_id=HGNC:11766 TGFB1]  
  |Structure =[http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?form=6&db=t&Dopt=s&uid=4850 Molecular structure]
| AltSymbols =TGFB, DPD1
| EntrezGene = 7040
| OMIM = 190180
| RefSeq = NM_000660
| UniProt = P01137
| PDB =  
| ECnumber =  
| Chromosome = 19
| Arm = q
| Band = 13.1
| LocusSupplementaryData =  
  |Review =
  |Type=TGF beta family
  |Functions=[[cell differentiation]], [[growth]], [[cell proliferation]]
  |Domains=  
  |Diseases=[[Camurati-Engelmann disease]] (CED) {{OMIM|131300}}, Modifier of [[Cystic fibrosis]]
  |Taxa = ''[[Homo sapiens]]''; homologs: many [[metazoan]] [[phylum (biology)|phyla]]
  | Cells = many
  | Location =[[extracellular]]
  |Mods=[[glycosylation]]
  |Names= '''TGF-beta-1'''
  |Interactions=
  |Pages=
}}


== Function ==
{{see also|TGF beta signaling pathway}}
TGF-β is a multifunctional set of peptides that controls [[cell proliferation|proliferation]], [[cellular differentiation|differentiation]], and other functions in many cell types. TGF-β acts synergistically with [[TGF alpha|TGFA]] in inducing [[tumorigenesis|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.<ref>{{cite web | title = Entrez Gene: TGFB1 transforming growth factor, beta 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7040| accessdate = }}</ref>


==Overview==
TGF-β1 was first identified in human [[platelet]]s as a protein with a molecular mass of 25 [[kilodalton]]s with a potential role in [[wound healing]].<ref>{{cite journal | vauthors = Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB | title = Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization | journal = J. Biol. Chem. | volume = 258 | issue = 11 | pages = 7155–60 | year = 1983 | pmid = 6602130 }}</ref> It was later characterized as a large [[protein precursor]] (containing 390 [[amino acid]]s) that was [[proteolysis|proteolytically]] processed to produce a mature peptide of 112 amino acids.<ref>{{cite journal | vauthors = Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV | title = Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells | journal = Nature | volume = 316 | issue = 6030 | pages = 701–5 | year = 1985 | pmid = 3861940 | doi = 10.1038/316701a0 }}</ref>
'''Transforming growth factor beta 1''' or '''TGF-β1''' is a polypeptide member of the [[transforming growth factor beta superfamily]] of [[cytokine]]s. It is a secreted protein that performs many cellular functions, including the control of [[cell growth]], [[cell proliferation]], [[cell differentiation]] and [[apoptosis]].  


TGF-β1 was first identified in human [[platelet]]s as a protein with a molecular mass of 25 [[kilodalton]]s with a potential role in [[wound healing]].<ref>{{cite journal |author=Assoian R, Komoriya A, Meyers C, Miller D, Sporn M |title=Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization |journal=J Biol Chem |volume=258 |issue=11 |pages=7155-60 |year=1983 |pmid=6602130}}</ref> It was later characterized as a large [[protein precursor]] (containing 390 [[amino acid]]s) that, was [[proteolysis|proteolytically]] processed to produce a mature peptide of 112 amino acids.<ref>{{cite journal |author=Derynck R, Jarrett J, Chen E, Eaton D, Bell J, Assoian R, Roberts A, Sporn M, Goeddel D |title=Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells |journal=Nature |volume=316 |issue=6030 |pages=701-5 |year=1985 |pmid=3861940}}</ref>
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 [[leukocyte]]s) secrete TGF-β1.<ref name = letter>{{cite journal | vauthors = Letterio JJ, Roberts AB | title = Regulation of immune responses by TGF-beta | journal = Annu. Rev. Immunol. | volume = 16 | issue = | pages = 137–61 | year = 1998 | pmid = 9597127 | doi = 10.1146/annurev.immunol.16.1.137 }}</ref>


TGF-β1 plays and important role in controlling the [[immune system]], and shows diiferent activities on different types of cell, or cells at different developmental stages. Most immune cells (or [[leukocyte]]s) secrete TGF-β1.<ref name = letter>{{cite journal |author=Letterio J, Roberts A |title=Regulation of immune responses by TGF-beta |journal=Annu Rev Immunol |volume=16 |issue= |pages=137-61 |year= |pmid=9597127}}</ref>
=== T cells===
Some [[T cell]]s (e.g. [[regulatory T cell]]s) release TGF-β1 to inhibit the actions of other T cells. [[Interleukin 1]]- and [[interleukin 2]]-dependent [[cell proliferation|proliferation]] of activated T cells,<ref>{{cite journal | vauthors = Wahl SM, Hunt DA, Wong HL, Dougherty S, McCartney-Francis N, Wahl LM, Ellingsworth L, Schmidt JA, Hall G, Roberts AB | title = Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation | journal = J. Immunol. | volume = 140 | issue = 9 | pages = 3026–32 | year = 1988 | pmid = 3129508 }}</ref><ref>{{cite journal | vauthors = Tiemessen MM, Kunzmann S, Schmidt-Weber CB, Garssen J, Bruijnzeel-Koomen CA, Knol EF, van Hoffen E | title = Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response | journal = Int. Immunol. | volume = 15 | issue = 12 | pages = 1495–504 | year = 2003 | pmid = 14645158 | doi = 10.1093/intimm/dxg147 }}</ref> and the activation of quiescent [[helper T cell]]s and [[cytotoxic T cell]]s is prevented by the activity of TGF-β1.<ref>{{cite journal | vauthors = Gilbert KM, Thoman M, Bauche K, Pham T, Weigle WO | title = Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in naive T cells | journal = Immunol. Invest. | volume = 26 | issue = 4 | pages = 459–72 | year = 1997 | pmid = 9246566 | doi = 10.3109/08820139709022702 }}</ref><ref name = Wahl>{{cite journal | vauthors = Wahl SM, Wen J, Moutsopoulos N | title = TGF-beta: a mobile purveyor of immune privilege | journal = Immunol. Rev. | volume = 213 | issue = | pages = 213–27 | year = 2006 | pmid = 16972906 | doi = 10.1111/j.1600-065X.2006.00437.x }}</ref>  Similarly, TGF-β1 can inhibit the secretion and activity of many other [[cytokine]]s including [[interferon-gamma|interferon-γ]], [[tumor necrosis factor-alpha]] (TNF-α) and various [[interleukin]]s.  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.<ref name="letter" />


===TGF-β1 and T cells===
=== B cells ===
Some [[T cell]]s (e.g. [[regulatory T cell]]s) release TGF-β1 to inhibit the actions of other T cells. [[Interleukin 1]]- and [[interleukin 2]]-dependent [[cell proliferation|proliferation]] of activated T cells,<ref>{{cite journal |author=Wahl S, Hunt D, Wong H, Dougherty S, McCartney-Francis N, Wahl L, Ellingsworth L, Schmidt J, Hall G, Roberts A |title=Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation |journal=J Immunol |volume=140 |issue=9 |pages=3026-32 |year=1988 |pmid=3129508}}</ref><ref>{{cite journal |author=Tiemessen M, Kunzmann S, Schmidt-Weber C, Garssen J, Bruijnzeel-Koomen C, Knol E, van Hoffen E |title=Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response |journal=Int Immunol |volume=15 |issue=12 |pages=1495-504 |year=2003 |pmid=14645158}}</ref> and the activation of quiescent [[helper T cell]]s and [[cytotoxic T cell]]s is prevented by the activity of TGF-β1.<ref>{{cite journal |author=Gilbert K, Thoman M, Bauche K, Pham T, Weigle W |title=Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in naive T cells |journal=Immunol Invest |volume=26 |issue=4 |pages=459-72 |year=1997 |pmid=9246566}}</ref><ref name = Wahl>{{cite journal |author=Wahl S, Wen J, Moutsopoulos N |title=TGF-beta: a mobile purveyor of immune privilege |journal=Immunol Rev |volume=213 |issue= |pages=213-27 |year=2006 |pmid=16972906}}</ref>  Similarly, TGF-β1 can inhibit the secretion and activity of many other [[cytokine]]s including [[interferon-gamma|interferon-γ]], [[tumor necrosis factor-alpha]] (TNF-α) and various [[interleukin]]s.  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.<ref>{{cite journal |author=Letterio J, Roberts A |title=Regulation of immune responses by TGF-beta |journal=Annu Rev Immunol |volume=16 |issue= |pages=137-61 |year=1998 |pmid=9597127}}</ref>
TGF-β1 has similar effects on [[B cell]]s that also vary according to the [[cell differentiation|differentiation]] state of the cell. It inhibits proliferation and stimulates [[apoptosis]] of B cells,<ref name = lebman>{{cite journal | vauthors = Lebman DA, Edmiston JS | title = The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes | journal = Microbes Infect. | volume = 1 | issue = 15 | pages = 1297–304 | year = 1999 | pmid = 10611758 | doi = 10.1016/S1286-4579(99)00254-3 }}</ref>  and plays a role in controlling the expression of [[antibody]], [[transferrin]] and [[MHC class II]] proteins on immature and mature B cells.<ref name = letter/><ref name = lebman/>


===TGF-β1 and B cells===
=== Myeloid cells ===
TGF-β1 has similar effects on [[B cell]]s that also vary according to the [[cell differentiation|differentiation]] state of the cell. It inhibits proliferation and [[apoptosis]] of B cells,<ref name = lebman>{{cite journal |author=Lebman D, Edmiston J |title=The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes |journal=Microbes Infect |volume=1 |issue=15 |pages=1297-304 |year=1999 |pmid=10611758}}</ref>  and plays a role in controlling the expression of [[antibody]], [[transferrin]] and [[MHC class II]] proteins on immature and mature B cells.<ref name = letter/><ref name = lebman/> 
The effects of TGF-β1 on [[macrophage]]s and [[monocyte]]s is predominantly suppressive; this cytokine can inhibit the proliferation of these cells and prevent their production of reactive oxygen (e.g. [[superoxide#Biology|superoxide (O<sub>2</sub><sup>&minus;</sup>)]]) and nitrogen (e.g. [[nitric oxide#Biological functions|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 [[pathogen]]s; 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 [[Tumor necrosis factor alpha|TNF-α]]),<ref name = Wahl/> and [[phagocytosis|phagocytic]] killing by macrophages can be increased by the action of TGF-β1.<ref name = letter/>


===TGF-β1 and myeloid cells===
TGF-β1 reduces the efficacy of the [[MHC II]] in [[astrocyte]]s and [[dendritic cell]]s, which in turn decreases the activation of appropriate [[helper T cell]] populations.<ref>{{cite journal | vauthors = Rodríguez LS, Narváez CF, Rojas OL, Franco MA, Ángel J | title = Human myeloid dendritic cells treated with supernatants of rotavirus infected Caco-2 cells induce a poor Th1 response | journal = Cellular Immunology | volume = 272 | issue = 2 | pages = 154–61 | date = 2012-01-01 | pmid = 22082567 | doi = 10.1016/j.cellimm.2011.10.017 | url = https://www.sciencedirect.com/science/article/abs/pii/S0008874911002784 }}</ref><ref>{{cite journal | vauthors = Dong Y, Tang L, Letterio JJ, Benveniste EN | title = The Smad3 protein is involved in TGF-beta inhibition of class II transactivator and class II MHC expression | journal = Journal of Immunology | volume = 167 | issue = 1 | pages = 311–9 | date = July 2001 | pmid = 11418665 | doi = 10.4049/jimmunol.167.1.311 }}</ref>
The effects of TGF-β1 on [[macrophage]]s and [[monocyte]]s is predominantly suppressive; this cytokine can inhibit the proliferation of these cells and prevent their production of reactive oxygen (e.g. [[superoxide#Biology and superoxide|superoxide (O<sub>2</sub><sup>&minus;</sup>]])) and nitrogen (e.g. [[nitric oxide#Biological functions|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 [[pathogen]]s; 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]]), <ref name = Wahl/> and [[phagocytosis|phagocytic]] killing by macrophages can be increased by the action of TGF-β1.<ref name = letter/>  


==References==
== Interactions ==
{{Reflist|2}}
TGF beta 1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[Decorin]],<ref name = pmid8093006>{{cite journal | vauthors = Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E | title = Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta | journal = Biochem. J. | volume = 302 | issue =  2| pages = 527–34  | date = September 1994 | pmid = 8093006 | pmc = 1137259 | doi =  10.1042/bj3020527}}</ref><ref name = pmid9675033>{{cite journal | vauthors = Schönherr E, Broszat M, Brandan E, Bruckner P, Kresse H | title = Decorin core protein fragment Leu155-Val260 interacts with TGF-beta but does not compete for decorin binding to type I collagen | journal = Arch. Biochem. Biophys. | volume = 355 | issue = 2 | pages = 241–8  | date = July 1998 | pmid = 9675033 | doi = 10.1006/abbi.1998.0720 }}</ref><ref name = pmid7798269>{{cite journal | vauthors = Takeuchi Y, Kodama Y, Matsumoto T | title = Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity | journal = J. Biol. Chem. | volume = 269 | issue = 51 | pages = 32634–8  | date = Dec 1994 | pmid = 7798269 | doi =  }}</ref>
* [[EIF3I]]<ref name = pmid9813058>{{cite journal | vauthors = Choy L, Derynck R | title = The type II transforming growth factor (TGF)-beta receptor-interacting protein TRIP-1 acts as a modulator of the TGF-beta response | journal = J. Biol. Chem. | volume = 273 | issue = 47 | pages = 31455–62  | date = November 1998 | pmid = 9813058 | doi =  10.1074/jbc.273.47.31455}}</ref>
* [[LTBP1 (gene)|LTBP1]],<ref name = pmid10930463>{{cite journal | vauthors = Saharinen J, Keski-Oja J | title = 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 | journal = Mol. Biol. Cell | volume = 11 | issue = 8 | pages = 2691–704  | date = August 2000 | pmid = 10930463 | pmc = 14949 | doi =  10.1091/mbc.11.8.2691}}</ref>
* [[TGF beta receptor 1]],<ref name = pmid8235612>{{cite journal | vauthors = Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R | title = Determination of type I receptor specificity by the type II receptors for TGF-beta or activin | journal = Science | volume = 262 | issue = 5135 | pages = 900–2  | date = November 1993 | pmid = 8235612 | doi =  10.1126/science.8235612}}</ref><ref name = pmid10716993>{{cite journal | vauthors = Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E | title = Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 6 | pages = 2626–31  | date = March 2000 | pmid = 10716993 | pmc = 15979 | doi =  10.1073/pnas.97.6.2626}}</ref>  and
* [[YWHAE]].<ref name = pmid11172812>{{cite journal | vauthors = McGonigle S, Beall MJ, Feeney EL, Pearce EJ | title = Conserved role for 14-3-3epsilon downstream of type I TGFbeta receptors | journal = FEBS Lett. | volume = 490 | issue = 1–2 | pages = 65–9  | date = February 2001 | pmid = 11172812 | doi =  10.1016/s0014-5793(01)02133-0}}</ref>
{{Div col end}}
{{clear}}
== References ==
{{Reflist|32em}}
 
== Further reading ==
{{Refbegin|32em}}
* {{cite journal | vauthors = Border WA, Noble NA | title = Transforming growth factor beta in tissue fibrosis | journal = N. Engl. J. Med. | volume = 331 | issue = 19 | pages = 1286–92 | year = 1994 | pmid = 7935686 | doi = 10.1056/NEJM199411103311907 }}
* {{cite journal | vauthors = Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB | title = Latent transforming growth factor-beta: structural features and mechanisms of activation | journal = Kidney Int. | volume = 51 | issue = 5 | pages = 1376–82 | year = 1997 | pmid = 9150447 | doi = 10.1038/ki.1997.188 }}
* {{cite journal | vauthors = Iozzo RV | title = The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins | journal = J. Biol. Chem. | volume = 274 | issue = 27 | pages = 18843–6 | year = 1999 | pmid = 10383378 | doi = 10.1074/jbc.274.27.18843 }}
* {{cite journal | vauthors = Reinhold D, Wrenger S, Kähne T, Ansorge S | title = HIV-1 Tat: immunosuppression via TGF-beta1 induction | journal = Immunol. Today | volume = 20 | issue = 8 | pages = 384–5 | year = 1999 | pmid = 10431160 | doi = 10.1016/S0167-5699(99)01497-8 }}
* {{cite journal | vauthors = Yamada Y | title = Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis | journal = Pharmacogenetics | volume = 11 | issue = 9 | pages = 765–71 | year = 2001 | pmid = 11740340 | doi = 10.1097/00008571-200112000-00004 }}
* {{cite book | vauthors = Chen W, Wahl SM | title = TGF-beta: receptors, signaling pathways and autoimmunity | journal = Curr. Dir. Autoimmun. | volume = 5 | issue =  | pages = 62–91 | year = 2002 | pmid = 11826761 | doi = 10.1159/000060548 | isbn = 978-3-8055-7308-5 | series = Current Directions in Autoimmunity }}
* {{cite journal | vauthors = Marone M, Bonanno G, Rutella S, Leone G, Scambia G, Pierelli L | title = Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21 | journal = Leuk. Lymphoma | volume = 43 | issue = 1 | pages = 51–7 | year = 2002 | pmid = 11908736 | doi = 10.1080/10428190210195 }}
* {{cite journal | vauthors = Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC | title = TGF-beta signal transduction and mesangial cell fibrogenesis | journal = Am. J. Physiol. Renal Physiol. | volume = 284 | issue = 2 | pages = F243–52 | year = 2003 | pmid = 12529270 | doi = 10.1152/ajprenal.00300.2002 }}
* {{cite journal | vauthors = Kalluri R, Neilson EG | title = Epithelial-mesenchymal transition and its implications for fibrosis | journal = J. Clin. Invest. | volume = 112 | issue = 12 | pages = 1776–84 | year = 2003 | pmid = 14679171 | pmc = 297008 | doi = 10.1172/JCI20530 }}
* {{cite journal | vauthors = Grainger DJ | title = Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis | journal = Arterioscler. Thromb. Vasc. Biol. | volume = 24 | issue = 3 | pages = 399–404 | year = 2004 | pmid = 14699019 | doi = 10.1161/01.ATV.0000114567.76772.33 }}
* {{cite journal | vauthors = Attisano L, Labbé E | title = TGFbeta and Wnt pathway cross-talk | journal = Cancer Metastasis Rev. | volume = 23 | issue = 1–2 | pages = 53–61 | year = 2004 | pmid = 15000149 | doi = 10.1023/A:1025811012690 }}
* {{cite journal | vauthors = McGowan TA, Zhu Y, Sharma K | title = Transforming growth factor-beta: a clinical target for the treatment of diabetic nephropathy | journal = Curr. Diab. Rep. | volume = 4 | issue = 6 | pages = 447–54 | year = 2004 | pmid = 15539010 | doi = 10.1007/s11892-004-0055-z }}
* {{cite journal | vauthors = Sheppard D | title = Integrin-mediated activation of latent transforming growth factor beta | journal = Cancer Metastasis Rev. | volume = 24 | issue = 3 | pages = 395–402 | year = 2005 | pmid = 16258727 | doi = 10.1007/s10555-005-5131-6 }}
* {{cite journal | vauthors = Gressner AM, Weiskirchen R | title = Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets | journal = J. Cell. Mol. Med. | volume = 10 | issue = 1 | pages = 76–99 | year = 2006 | pmid = 16563223 | pmc = 3933103 | doi = 10.1111/j.1582-4934.2006.tb00292.x }}
* {{cite journal | vauthors = Seoane J | title = Escaping from the TGFbeta anti-proliferative control | journal = Carcinogenesis | volume = 27 | issue = 11 | pages = 2148–56 | year = 2006 | pmid = 16698802 | doi = 10.1093/carcin/bgl068 }}
* {{cite journal | vauthors = Lee CG, Kang HR, Homer RJ, Chupp G, Elias JA | title = Transgenic modeling of transforming growth factor-beta(1): role of apoptosis in fibrosis and alveolar remodeling | journal = Proc Am Thorac Soc | volume = 3 | issue = 5 | pages = 418–23 | year = 2006 | pmid = 16799085 | pmc = 2658706 | doi = 10.1513/pats.200602-017AW }}
* {{cite journal | vauthors = Wahl SM | title = Transforming growth factor-beta: innately bipolar | journal = Curr. Opin. Immunol. | volume = 19 | issue = 1 | pages = 55–62 | year = 2007 | pmid = 17137775 | doi = 10.1016/j.coi.2006.11.008 }}
* {{cite journal | vauthors = Redondo S, Santos-Gallego CG, Tejerina T | title = TGF-beta1: a novel target for cardiovascular pharmacology | journal = Cytokine Growth Factor Rev. | volume = 18 | issue = 3–4 | pages = 279–86 | year = 2007 | pmid = 17485238 | doi = 10.1016/j.cytogfr.2007.04.005 }}
{{Refend}}
 
{{PDB Gallery|geneid=7040}}


{{TGF beta signaling}}
{{TGF beta signaling}}
{{Growth factors}}
{{TGFβ receptor superfamily modulators}}


[[Category:Proteins]]
[[Category:Proteins]]
[[Category:TGFβ domain]]
[[Category:TGFβ domain]]
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Latest revision as of 17:53, 15 December 2018

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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

See also: TGF beta signaling pathway

TGF-β is a multifunctional set of peptides that controls proliferation, differentiation, and other functions in many cell types. TGF-β acts synergistically with TGFA 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] 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]

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.[6]

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 stimulates apoptosis of B cells,[11] and plays a role in controlling the expression of antibody, transferrin and MHC class II proteins on immature and mature B cells.[6][11]

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]

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.[12][13]

Interactions

TGF beta 1 has been shown to interact with:

References

  1. ↑ Ghadami M, Makita Y, Yoshida K, Nishimura G, Fukushima Y, Wakui K, Ikegawa S, Yamada K, Kondo S, Niikawa N, Tomita Ha (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. PMC 1288319. 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".
  4. ↑ Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB (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 JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV (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. ↑ 6.0 6.1 6.2 6.3 Letterio JJ, Roberts AB (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 SM, Hunt DA, Wong HL, Dougherty S, McCartney-Francis N, Wahl LM, Ellingsworth L, Schmidt JA, Hall G, Roberts AB (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 MM, Kunzmann S, Schmidt-Weber CB, Garssen J, Bruijnzeel-Koomen CA, Knol EF, 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 KM, Thoman M, Bauche K, Pham T, Weigle WO (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. ↑ 10.0 10.1 Wahl SM, 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. ↑ 11.0 11.1 Lebman DA, Edmiston JS (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.
  12. ↑ Rodríguez LS, Narváez CF, Rojas OL, Franco MA, Ángel J (2012-01-01). "Human myeloid dendritic cells treated with supernatants of rotavirus infected Caco-2 cells induce a poor Th1 response". Cellular Immunology. 272 (2): 154–61. doi:10.1016/j.cellimm.2011.10.017. PMID 22082567.
  13. ↑ Dong Y, Tang L, Letterio JJ, Benveniste EN (July 2001). "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. doi:10.4049/jimmunol.167.1.311. PMID 11418665.
  14. ↑ Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E (September 1994). "Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta". Biochem. J. 302 (2): 527–34. doi:10.1042/bj3020527. PMC 1137259. PMID 8093006.
  15. ↑ Schönherr E, Broszat M, Brandan E, Bruckner P, Kresse H (July 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. 355 (2): 241–8. doi:10.1006/abbi.1998.0720. PMID 9675033.
  16. ↑ Takeuchi Y, Kodama Y, Matsumoto T (Dec 1994). "Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity". J. Biol. Chem. 269 (51): 32634–8. PMID 7798269.
  17. ↑ Choy L, Derynck R (November 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. 273 (47): 31455–62. doi:10.1074/jbc.273.47.31455. PMID 9813058.
  18. ↑ Saharinen J, Keski-Oja J (August 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. 11 (8): 2691–704. doi:10.1091/mbc.11.8.2691. PMC 14949. PMID 10930463.
  19. ↑ Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R (November 1993). "Determination of type I receptor specificity by the type II receptors for TGF-beta or activin". Science. 262 (5135): 900–2. doi:10.1126/science.8235612. PMID 8235612.
  20. ↑ Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (March 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. 97 (6): 2626–31. doi:10.1073/pnas.97.6.2626. PMC 15979. PMID 10716993.
  21. ↑ McGonigle S, Beall MJ, Feeney EL, Pearce EJ (February 2001). "Conserved role for 14-3-3epsilon downstream of type I TGFbeta receptors". FEBS Lett. 490 (1–2): 65–9. doi:10.1016/s0014-5793(01)02133-0. PMID 11172812.

Further reading

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