TGF beta 1

TGFB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KLA, 1KLC, 1KLD, 3KFD, 4KV5
Identifiers
Aliases	TGFB1, CED, DPD1, LAP, TGFB, TGFbeta, transforming growth factor beta 1, IBDIMDE, TGF-beta1
External IDs	OMIM: 190180; MGI: 98725; HomoloGene: 540; GeneCards: TGFB1; OMA:TGFB1 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.2 Start 41,301,587 bp End 41,353,922 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7 A3|7 13.98 cM Start 25,386,427 bp End 25,404,502 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte stromal cell of endometrium ascending aorta Descending thoracic aorta right coronary artery spleen right lung canal of the cervix blood Top expressed in molar tibiofemoral joint stroma of bone marrow granulocyte calvaria mesenteric lymph nodes spleen lower jaw thymus body of femur More reference expression data BioGPS More reference expression data
Gene ontology Molecular function type II transforming growth factor beta receptor binding protein N-terminus binding cytokine activity enzyme binding growth factor activity antigen binding type I transforming growth factor beta receptor binding protein homodimerization activity protein serine/threonine kinase activator activity protein binding protein heterodimerization activity type III transforming growth factor beta receptor binding transforming growth factor beta receptor binding identical protein binding Cellular component cytoplasm extracellular region nucleus microvillus cell surface blood microparticle plasma membrane secretory granule axon soma Golgi lumen platelet alpha granule lumen extracellular matrix extracellular space Biological process positive regulation of histone deacetylation positive regulation of transcription regulatory region DNA binding ureteric bud development tolerance induction to self antigen positive regulation of protein phosphorylation endoderm development response to cholesterol positive regulation of MAP kinase activity regulation of sodium ion transport response to progesterone negative regulation of cell cycle response to organic substance mammary gland development T cell homeostasis negative regulation of ossification negative regulation of hyaluronan biosynthetic process protein phosphorylation T cell differentiation positive regulation of vascular permeability animal organ regeneration positive regulation of blood vessel endothelial cell migration negative regulation of epithelial cell proliferation regulation of binding inner ear development myelination negative regulation of macrophage cytokine production cell population proliferation transforming growth factor beta receptor signaling pathway face morphogenesis negative regulation of cell population proliferation positive regulation of receptor clustering regulation of apoptotic process positive regulation of collagen biosynthetic process cellular response to transforming growth factor beta stimulus pathway-restricted SMAD protein phosphorylation regulation of DNA binding regulation of actin cytoskeleton reorganization negative regulation of fat cell differentiation positive regulation of protein metabolic process cell-cell junction organization negative regulation of myoblast differentiation positive regulation of protein kinase B signaling common-partner SMAD protein phosphorylation positive regulation of branching involved in ureteric bud morphogenesis SMAD protein signal transduction epidermal growth factor receptor signaling pathway macrophage derived foam cell differentiation negative regulation of blood vessel endothelial cell migration positive regulation of protein dephosphorylation extrinsic apoptotic signaling pathway negative regulation of extracellular matrix disassembly mitotic cell cycle checkpoint signaling positive regulation of fibroblast proliferation negative regulation of cell differentiation regulation of branching involved in mammary gland duct morphogenesis positive regulation of exit from mitosis negative regulation of transforming growth factor beta receptor signaling pathway negative regulation of gene expression morphogenesis of a branching structure regulation of SMAD protein signal transduction positive regulation of peptidyl-serine phosphorylation cell activation negative regulation of neuroblast proliferation positive regulation of transcription, DNA-templated cell growth negative regulation of T cell proliferation response to wounding negative regulation of cell growth positive regulation of chemotaxis protein export from nucleus regulation of protein import into nucleus positive regulation of peptidyl-tyrosine phosphorylation positive regulation of protein import into nucleus positive regulation of cardiac muscle cell differentiation oligodendrocyte development positive regulation of interleukin-17 production inflammatory response negative regulation of interleukin-17 production lymph node development T cell activation Notch signaling pathway negative regulation of protein phosphorylation regulation of blood vessel remodeling SMAD protein complex assembly regulation of striated muscle tissue development response to vitamin D chondrocyte differentiation regulatory T cell differentiation regulation of cartilage development branch elongation involved in mammary gland duct branching positive regulation of bone mineralization positive regulation of epithelial cell proliferation female pregnancy cellular response to organic cyclic compound positive regulation of extracellular matrix assembly cellular calcium ion homeostasis wound healing negative regulation of transcription by RNA polymerase II response to glucose positive regulation of epithelial to mesenchymal transition cellular response to dexamethasone stimulus negative regulation of production of miRNAs involved in gene silencing by miRNA mitigation of host defenses by virus lens fiber cell differentiation positive regulation of NF-kappaB transcription factor activity extracellular matrix assembly ATP biosynthetic process hematopoietic progenitor cell differentiation regulation of interleukin-23 production positive regulation of protein secretion frontal suture morphogenesis epithelial to mesenchymal transition phosphate-containing compound metabolic process regulation of gene expression adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains negative regulation of release of sequestered calcium ion into cytosol response to radiation mononuclear cell proliferation negative regulation of transcription, DNA-templated negative regulation of T cell activation positive regulation of odontogenesis lipopolysaccharide-mediated signaling pathway positive regulation of protein localization to nucleus response to estradiol regulation of cell migration response to hypoxia hyaluronan catabolic process negative regulation of phagocytosis response to organic cyclic compound positive regulation of protein-containing complex assembly protein kinase B signaling negative regulation of cell-cell adhesion negative regulation of gene silencing by miRNA positive regulation of regulatory T cell differentiation cellular response to growth factor stimulus positive regulation of pathway-restricted SMAD protein phosphorylation mammary gland branching involved in thelarche response to laminar fluid shear stress human ageing regulation of regulatory T cell differentiation platelet degranulation negative regulation of DNA replication myeloid dendritic cell differentiation salivary gland morphogenesis receptor catabolic process MAPK cascade positive regulation of histone acetylation regulation of transforming growth factor beta receptor signaling pathway positive regulation of phosphatidylinositol 3-kinase activity negative regulation of protein localization to plasma membrane positive regulation of NAD+ ADP-ribosyltransferase activity negative regulation of immune response regulation of cell population proliferation negative regulation of skeletal muscle tissue development positive regulation of peptidyl-threonine phosphorylation positive regulation of smooth muscle cell differentiation positive regulation of isotype switching to IgA isotypes connective tissue replacement involved in inflammatory response wound healing ossification involved in bone remodeling positive regulation of apoptotic process positive regulation of vascular endothelial growth factor production positive regulation of superoxide anion generation digestive tract development cell migration positive regulation of fibroblast migration positive regulation of cell division germ cell migration positive regulation of transcription by RNA polymerase II negative regulation of mitotic cell cycle positive regulation of SMAD protein signal transduction positive regulation of pri-miRNA transcription by RNA polymerase II positive regulation of gene expression positive regulation of cell population proliferation liver regeneration regulation of epithelial to mesenchymal transition involved in endocardial cushion formation positive regulation of mononuclear cell migration cellular response to insulin-like growth factor stimulus positive regulation of cell migration response to immobilization stress cellular response to mechanical stimulus cellular response to ionizing radiation vasculogenesis neural tube closure heart valve morphogenesis heart development neural tube development membrane protein intracellular domain proteolysis leukocyte migration ventricular cardiac muscle tissue morphogenesis positive regulation of ERK1 and ERK2 cascade transforming growth factor beta receptor signaling pathway involved in heart development embryonic liver development BMP signaling pathway cell development apoptotic process regulation of pri-miRNA transcription by RNA polymerase II positive regulation of production of miRNAs involved in gene silencing by miRNA regulation of signaling receptor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7040 21803 Ensembl ENSG00000105329 ENSMUSG00000002603 UniProt P01137 P04202 RefSeq (mRNA) NM_000660 NM_011577 RefSeq (protein) NP_000651 NP_035707 Location (UCSC) Chr 19: 41.3 – 41.35 Mb Chr 7: 25.39 – 25.4 Mb PubMed search
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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.

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 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.

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. 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.

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.

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, as well as the activation of quiescent helper T cells and cytotoxic T cells. 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.

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, and controls the expression of antibody, transferrin and MHC class II proteins on immature and mature B cells.

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), and macrophage's phagocytic can be increased by the action of TGF-β1.

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.

Interactions

TGF beta 1 has been shown to interact with:

• Decorin,
• EIF3I
• LTBP1,
• TGF beta receptor 1, and
• YWHAE.

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, Mazzieri R, Nunes I, Rifkin DB (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 (2001). "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-β: Receptors, Signaling Pathways and Autoimmunity". TGF-beta: receptors, signaling pathways and autoimmunity. Current Directions in Autoimmunity. Vol. 5. pp. 62–91. doi:10.1159/000060548. ISBN 978-3-8055-7308-5. PMID 11826761. {{cite book}}: |journal= ignored (help)
• Marone M, Bonanno G, Rutella S, Leone G, Scambia G, Pierelli L (2002). "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. S2CID 28490341.
• 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. S2CID 17046094.
• Kalluri R, Neilson EG (2003). "Epithelial-mesenchymal transition and its implications for fibrosis". J. Clin. Invest. 112 (12): 1776–84. doi:10.1172/JCI20530. PMC 297008. PMID 14679171.
• Grainger DJ (2004). "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. S2CID 41685620.
• McGowan TA, Zhu Y, Sharma K (2004). "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. S2CID 45122439.
• Sheppard D (2005). "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. S2CID 1929903.
• 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. PMC 3933103. 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, Chupp G, Elias JA (2006). "Transgenic modeling of transforming growth factor-beta(1): role of apoptosis in fibrosis and alveolar remodeling". Proc Am Thorac Soc. 3 (5): 418–23. doi:10.1513/pats.200602-017AW. PMC 2658706. 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.
• Ren H, Han R, Chen X, Liu X, Wan J, Wang L, Yang X, Wang J (May 2020). "Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update". J Cereb Blood Flow Metab. 40 (9): 1752–1768. doi:10.1177/0271678X20923551. PMC 7446569. PMID 32423330. S2CID 218689863.

External links

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