TGF beta 1

Transforming growth factor, beta 1

PDB rendering based on 1kla.

Available structures
PDB	1KLA, 1KLC, 1KLD, 3KFD

Identifiers

Symbols

TGFB1; CED; DPD1; LAP; TGFB; TGFbeta

External IDs

OMIM: 190180 MGI: 98725 HomoloGene: 540 GeneCards: TGFB1 Gene

Gene Ontology
Molecular function	• type II transforming growth factor beta receptor binding • type II transforming growth factor beta receptor binding • transforming growth factor beta receptor binding • protein binding • growth factor activity • protein homodimerization activity • protein heterodimerization activity • protein N-terminus binding
Cellular component	• extracellular region • extracellular region • proteinaceous extracellular matrix • extracellular space • nucleus • cytoplasm • Golgi lumen • Golgi lumen • cell surface • stored secretory granule • axon • platelet alpha granule lumen • neuronal cell body
Biological process	• protein import into nucleus, translocation • negative regulation of transcription from RNA polymerase II promoter • ureteric bud development • response to hypoxia • morphogenesis of a branching structure • negative regulation of protein phosphorylation • positive regulation of protein phosphorylation • regulation of sodium ion transport • chondrocyte differentiation • hemopoietic progenitor cell differentiation • connective tissue replacement involved in inflammatory response wound healing • adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains • tolerance induction to self antigen • platelet degranulation • protein phosphorylation • protein export from nucleus • ATP biosynthetic process • phosphate metabolic process • cellular calcium ion homeostasis • induction of apoptosis • inflammatory response • cell cycle arrest • epidermal growth factor receptor signaling pathway • transforming growth factor beta receptor signaling pathway • transforming growth factor beta receptor signaling pathway • transforming growth factor beta receptor signaling pathway • SMAD protein complex assembly • SMAD protein import into nucleus • negative regulation of neuroblast proliferation • salivary gland morphogenesis • endoderm development • female pregnancy • aging • blood coagulation • negative regulation of DNA replication • cell death • positive regulation of cell proliferation • positive regulation of cell proliferation • negative regulation of cell proliferation • germ cell migration • response to radiation • response to wounding • response to glucose stimulus • embryo development • defense response to fungus, incompatible interaction • positive regulation of gene expression • positive regulation of epithelial to mesenchymal transition • macrophage derived foam cell differentiation • positive regulation of fibroblast migration • positive regulation of peptidyl-threonine phosphorylation • positive regulation of pathway-restricted SMAD protein phosphorylation • negative regulation of macrophage cytokine production • response to organic cyclic compound • regulation of striated muscle tissue development • regulation of transforming growth factor beta receptor signaling pathway • virus-host interaction • evasion of host defenses by virus • viral infectious cycle • negative regulation of cell-cell adhesion • platelet activation • negative regulation of ossification • negative regulation of cell growth • regulation of cell migration • positive regulation of bone mineralization • mammary gland development • positive regulation of histone deacetylation • organ regeneration • positive regulation of exit from mitosis • mitotic cell cycle G1/S transition checkpoint • positive regulation of cellular protein metabolic process • response to estradiol stimulus • response to progesterone stimulus • positive regulation of interleukin-17 production • receptor catabolic process • mononuclear cell proliferation • positive regulation of collagen biosynthetic process • positive regulation of collagen biosynthetic process • positive regulation of peptidyl-serine phosphorylation • response to vitamin D • response to laminar fluid shear stress • positive regulation of histone acetylation • positive regulation of protein dephosphorylation • negative regulation of T cell proliferation • regulation of protein import into nucleus • positive regulation of odontogenesis • response to drug • myelination • myeloid dendritic cell differentiation • T cell homeostasis • positive regulation of MAP kinase activity • positive regulation of blood vessel endothelial cell migration • negative regulation of blood vessel endothelial cell migration • positive regulation of phosphatidylinositol 3-kinase activity • ossification involved in bone remodeling • regulatory T cell differentiation • cell-cell junction organization • negative regulation of fat cell differentiation • negative regulation of cell cycle • negative regulation of transcription, DNA-dependent • positive regulation of transcription, DNA-dependent • positive regulation of transcription, DNA-dependent • negative regulation of mitotic cell cycle • positive regulation of transcription from RNA polymerase II promoter • active induction of host immune response by virus • positive regulation of isotype switching to IgA isotypes • lymph node development • digestive tract development • inner ear development • positive regulation of epithelial cell proliferation • negative regulation of epithelial cell proliferation • positive regulation of protein secretion • negative regulation of phagocytosis • negative regulation of immune response • positive regulation of chemotaxis • positive regulation of NF-kappaB transcription factor activity • regulation of binding • regulation of DNA binding • positive regulation of smooth muscle cell differentiation • negative regulation of release of sequestered calcium ion into cytosol • positive regulation of cell division • response to protein stimulus • positive regulation of protein kinase B signaling cascade • frontal suture morphogenesis • pathway-restricted SMAD protein phosphorylation • positive regulation of SMAD protein import into nucleus • mammary gland branching involved in thelarche • branch elongation involved in mammary gland duct branching • regulation of branching involved in mammary gland duct morphogenesis • lens fiber cell differentiation • response to cholesterol • positive regulation of cell cycle arrest • cellular response to growth factor stimulus • cellular response to dexamethasone stimulus • positive regulation of branching involved in ureteric bud morphogenesis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
41.84 – 41.86 Mb

Chr 7:
26.47 – 26.49 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]

1 Function
2 Interactions
3 References
4 Further reading

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]

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.^[6]

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 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]

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,^[12]^[13] LTBP1,^[14] YWHAE,^[15] EIF3I^[16] and Decorin.^[17]^[18]^[19]

References

^ 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. PMC 1288319. PMID 10631145. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1288319.
^ 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.
^ "Entrez Gene: TGFB1 transforming growth factor, beta 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7040.
^ 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.
^ 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.
^ ^a ^b ^c ^d 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.
^ 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.
^ 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.
^ 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.
^ ^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.
^ ^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.
^ 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. doi:10.1126/science.8235612. ISSN 0036-8075. PMID 8235612.
^ 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-β1 signaling in the regulation of angiogenesis". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (6): 2626–31. doi:10.1073/pnas.97.6.2626. ISSN 0027-8424. PMC 15979. PMID 10716993. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15979.
^ Saharinen, J; Keski-Oja J (Aug. 2000). "Specific Sequence Motif of 8-Cys Repeats of TGF-β Binding Proteins, LTBPs, Creates a Hydrophobic Interaction Surface for Binding of Small Latent TGF-β". Mol. Biol. Cell (UNITED STATES) 11 (8): 2691–704. ISSN 1059-1524. PMC 14949. PMID 10930463. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=14949.
^ 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. doi:10.1016/S0014-5793(01)02133-0. ISSN 0014-5793. PMID 11172812.
^ 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. doi:10.1074/jbc.273.47.31455. ISSN 0021-9258. PMID 9813058.
^ 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) (Pt 2): 527–34. ISSN 0264-6021. PMC 1137259. PMID 8093006. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1137259.
^ 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.
^ 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.

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.. Current Directions in Autoimmunity 5: 62–91. doi:10.1159/000060548. ISBN 3-8055-7308-1. 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/JCI20530. PMC 297008. PMID 14679171. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=297008.
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-β1: Role of Apoptosis in Fibrosis and Alveolar Remodeling". Proceedings of the American Thoracic Society 3 (5): 418–23. doi:10.1513/pats.200602-017AW. PMC 2658706. PMID 16799085. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2658706.
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PDB gallery

1kla: SOLUTION STRUCTURE OF TGF-B1, NMR, MODELS 1-17 OF 33 STRUCTURES

1klc: SOLUTION STRUCTURE OF TGF-B1, NMR, MINIMIZED AVERAGE STRUCTURE

1kld: SOLUTION STRUCTURE OF TGF-B1, NMR, MODELS 18-33 OF 33 STRUCTURES

Cell signaling: TGF beta signaling pathway

TGF beta superfamily of ligands	TGF beta family (TGF-β1, TGF-β2, TGF-β3) Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15) Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15) Other (Activin and inhibin, Anti-müllerian hormone, Nodal)

TGF beta receptors (Activin, BMP)	TGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) · ACVRL1 · BMPR1 (BMPR1A · BMPR1B) TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) · AMHR2 · BMPR2 TGFBR3: betaglycan

Transducers/SMAD	R-SMAD (SMAD1, SMAD2, SMAD3, SMAD5, SMAD9) · I-SMAD (SMAD6, SMAD7) · SMAD4

Ligand inhibitors	Cerberus · Chordin · DAN · Decorin · Follistatin · Gremlin · Lefty · LTBP1 · Noggin · THBS1

Coreceptors	BAMBI · Cripto

Other	SARA

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

Growth factors

Fibroblast	FGF receptor ligands: FGF1/FGF2/FGF5 · FGF3/FGF4/FGF6 · KGF (FGF7/FGF10/FGF22) · FGF8/FGF17/FGF18 · FGF9/FGF16/FGF20 FGF homologous factors: FGF11 · FGF12 · FGF13 · FGF14 hormone-like: FGF19 · FGF21 · FGF23

EGF-like domain	TGF-α · EGF · HB-EGF

TGFβ pathway	TGF-β (TGF-β1, TGF-β2, TGF-β3)

Insulin-like	IGF-1 · IGF-2

Platelet-derived	PDGFA · PDGFB · PDGFC · PDGFD

Vascular endothelial	VEGF-A · VEGF-B · VEGF-C · VEGF-D · PGF

Other	Nerve · Hepatocyte

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)