TGF-β1

TGFB1
PDBに登録されている構造 PDB オルソログ検索: RCSB PDBe PDBj PDBのIDコード一覧 1KLA, 1KLC, 1KLD, 3KFD, 4KV5
識別子
記号	TGFB1, CED, DPD1, LAP, TGFB, TGFbeta, transforming growth factor beta 1, IBDIMDE, TGF-beta1
外部ID	OMIM: 190180 MGI: 98725 HomoloGene: 540 GeneCards: TGFB1
遺伝子の位置 (ヒト) 染色体 19番染色体 (ヒト)[1] バンド データ無し 開始点 41,301,587 bp[1] 終点 41,353,922 bp[1]
遺伝子の位置 (マウス) 染色体 7番染色体 (マウス)[2] バンド データ無し 開始点 25,386,427 bp[2] 終点 25,404,502 bp[2]
RNA発現パターン さらなる参照発現データ
遺伝子オントロジー 分子機能 • type II transforming growth factor beta receptor binding • protein N-terminus binding • cytokine activity • 酵素結合 • growth factor activity • 抗原結合 • type I transforming growth factor beta receptor binding • protein homodimerization activity • protein serine/threonine kinase activator activity • 血漿タンパク結合 • protein heterodimerization activity • type III transforming growth factor beta receptor binding • transforming growth factor beta receptor binding • identical protein binding 細胞の構成要素 • 細胞質 • 細胞外領域 • 細胞核 • 微絨毛 • cell surface • blood microparticle • 細胞膜 • secretory granule • 神経繊維 • soma • Golgi lumen • platelet alpha granule lumen • 細胞外マトリックス • 細胞外空間 生物学的プロセス • 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 • 内胚葉の発生 • response to cholesterol • positive regulation of MAP kinase activity • regulation of sodium ion transport • response to progesterone • negative regulation of cell cycle • 有機物への反応 • 乳房発達 • T cell homeostasis • negative regulation of ossification • negative regulation of hyaluronan biosynthetic process • タンパク質リン酸化 • 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 • 細胞増殖 • 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 • 遺伝子発現の負の調節 • 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 • 細胞増殖 • 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 • 炎症反応 • negative regulation of interleukin-17 production • リンパ節発生 • T cell activation • Notchシグナリング • 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 • 傷の治癒 • negative regulation of transcription by RNA polymerase II • response to glucose • positive regulation of epithelial to mesenchymal transition • デキサメタゾン刺激に対する細胞応答 • 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 • 上皮間葉転換 • リン酸を含む化合物の代謝プロセス • 遺伝子発現調節 • 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 • リポ多糖を介したシグナル伝達経路 • positive regulation of protein localization to nucleus • エストラジオールへの反応 • regulation of cell migration • 低酸素症への反応 • hyaluronan catabolic process • negative regulation of phagocytosis • 有機環状化合物への反応 • positive regulation of protein-containing complex assembly • Akt/PKBシグナル経路 • 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 • 老化 • 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 • 消化管発生 • 遊走 • 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 • 脈管形成 • neural tube closure • heart valve morphogenesis • 心臓発生 • 神経管発生 • 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 • 細胞発生 • アポトーシス • 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 出典:Amigo / QuickGO
オルソログ
種	ヒト	マウス
Entrez	7040	21803
Ensembl	ENSG00000105329	ENSMUSG00000002603
UniProt	P01137	P04202
RefSeq (mRNA)	NM_000660	NM_011577
RefSeq (タンパク質)	NP_000651	NP_035707
場所 (UCSC)	Chr 19: 41.3 – 41.35 Mb	Chr 19: 25.39 – 25.4 Mb
PubMed検索	[3]	[4]
ウィキデータ
閲覧/編集 ヒト 閲覧/編集 マウス

TGF-β1（transforming growth factor beta 1）は、TGF-βスーパーファミリーに属するサイトカインの1つであり、細胞成長、細胞増殖、細胞分化、アポトーシスの制御など、多くの細胞機能を発揮する分泌タンパク質である。ヒトでは、TGF-β1はTGFB1遺伝子にコードされる^[5][6]。

機能

→「TGF-βシグナル伝達経路（英語版）」も参照

TGF-βは、多くの細胞種において増殖、分化やその他の機能を制御する多機能型ペプチド群である。形質転換の誘導においては、TGF-βはTGF-αと相乗的に機能する。また、成長を負に制御する自己分泌型成長因子でもある。TGF-βの活性化やシグナル伝達の調節不全によって、アポトーシスが引き起こされる可能性がある。多くの細胞がTGF-βを合成し、そのほぼ全てで対応する特異的受容体が発現している。TGF-β1、TGF-β2（英語版）、TGF-β3（英語版）は全て同じ受容体を介して機能する^[7]。

TGF-β1は、ヒトの血小板において創傷治癒に関与している可能性のある25 kDaのタンパク質として最初に同定された^[8][9]。その後、大きな前駆体タンパク質（390アミノ酸）がタンパク質切断によって112アミノ酸の成熟ペプチドへとプロセシングされたものであることが明らかにされた^[10]。

TGF-β1は免疫系の制御に重要な役割を果たしており、細胞の種類やその発生段階によって異なる活性を示すことが示されている。大部分の免疫細胞（白血球）がTGF-β1を分泌していることが知られている^[11]。

T細胞

一部のT細胞（制御性T細胞など）はTGF-β1を放出して他のT細胞の作用を阻害している。具体的には、TGF-β1は活性化されたT細胞のIL-1とIL-2に依存的な増殖や^[12][13]、静止状態のヘルパーT細胞や細胞傷害性T細胞の活性化を阻害する^[14][15]。同様にTGF-β1は、IFN-γ、TNF-αなど他の多くのサイトカインやさまざまなインターロイキンの分泌と活性を阻害する。また、IL-2受容体（英語版）などのサイトカイン受容体（英語版）の発現レベルを低下させ、免疫細胞の活性をダウンレギュレーションする。一方でTGF-β1は、特に未成熟なT細胞に対しては、特定のサイトカインの発現上昇をもたらし、その増殖を促進する場合もある^[11][16]。

B細胞

TGF-β1はB細胞にも同様の影響を及ぼし、この作用もまた細胞の分化状態によって異なる。B細胞の増殖を阻害してアポトーシスを刺激し^[17]、また未成熟型・成熟型B細胞上への抗体、トランスフェリン、MHCクラスII分子の発現を制御する^[11][17]。

骨髄系細胞

マクロファージや単球へのTGF-β1の作用は、主に抑制的なものである。このサイトカインはこれらの細胞の増殖を阻害し、活性酸素種（スーパーオキシド（O₂⁻）など）や活性窒素種（一酸化窒素（NO）など）の産生を阻害する。また、TGF-β1は骨髄由来の細胞に対して反対の作用を及ぼす場合もある。例えば、TGF-β1は化学誘引物質として作用し、特定の病原体に対する免疫応答を指示する。同様に、マクロファージや単球は低濃度のTGF-β1に対する走化性応答を示す。さらに、単球のサイトカインの発現（IL-1α（英語版）、IL-1β、TNF-αなど）やマクロファージの食作用はTGF-β1の作用によって増大する^[11]。

TGF-β1はアストロサイトや樹状細胞のMHCクラスII分子の発現を低下させ、それによってヘルパーT細胞集団の活性化を低下させる^[18][19]。

相互作用

TGF-β1は次に挙げる因子と相互作用することが示されている。

• デコリン（英語版）^[20][21][22]
• EIF3I（英語版）^[23]
• LTBP1（英語版）^[24]
• TGFBR1（英語版）^[25][26]
• YWHAE（英語版）^[27]

出典

1. ^ GRCh38: Ensembl release 89: ENSG00000105329 - Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000002603 - Ensembl, May 2017
3. Human PubMed Reference:
4. Mouse PubMed Reference:
5. “Genetic mapping of the Camurati-Engelmann disease locus to chromosome 19q13.1-q13.3”. Am. J. Hum. Genet. 66 (1): 143–7. (January 2000). doi:10.1086/302728. PMC 1288319. PMID 10631145. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288319/. 
6. “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. (May 2000). doi:10.1006/geno.2000.6192. PMID 10843814. 
7. “Entrez Gene: TGFB1 transforming growth factor, beta 1”. 11 March 2009閲覧。
8. “Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization”. J. Biol. Chem. 258 (11): 7155–60. (1983). doi:10.1016/S0021-9258(18)32345-7. PMID 6602130. 
9. Custo, S; Baron, B; Felice, A; Seria, E (5 July 2022). “A comparative profile of total protein and six angiogenically-active growth factors in three platelet products”. GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW 11 (Doc06): Doc06. doi:10.3205/iprs000167. PMC 9284722. PMID 35909816. https://www.egms.de/static/en/journals/iprs/2022-11/iprs000167.shtml#block5. 
10. “Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells”. Nature 316 (6030): 701–5. (1985). Bibcode: 1985Natur.316..701D. doi:10.1038/316701a0. PMID 3861940. https://zenodo.org/record/1233037. 
11. ^ “Regulation of immune responses by TGF-beta”. Annu. Rev. Immunol. 16: 137–61. (1998). doi:10.1146/annurev.immunol.16.1.137. PMID 9597127. https://zenodo.org/record/1234983. 
12. “Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation”. J. Immunol. 140 (9): 3026–32. (1988). doi:10.4049/jimmunol.140.9.3026. PMID 3129508. 
13. “Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response”. Int. Immunol. 15 (12): 1495–504. (2003). doi:10.1093/intimm/dxg147. PMID 14645158. 
14. “Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in naive T cells”. Immunol. Invest. 26 (4): 459–72. (1997). doi:10.3109/08820139709022702. PMID 9246566. 
15. “TGF-beta: a mobile purveyor of immune privilege”. Immunol. Rev. 213: 213–27. (2006). doi:10.1111/j.1600-065X.2006.00437.x. PMID 16972906. https://zenodo.org/record/1230716. 
16. “Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage”. Prog. Neurobiol. 178: 101610. (March 2019). doi:10.1016/j.pneurobio.2019.03.003. PMID 30923023. 
17. ^ “The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes”. Microbes Infect. 1 (15): 1297–304. (1999). doi:10.1016/S1286-4579(99)00254-3. PMID 10611758. 
18. “Human myeloid dendritic cells treated with supernatants of rotavirus infected Caco-2 cells induce a poor Th1 response”. Cellular Immunology 272 (2): 154–61. (2012-01-01). doi:10.1016/j.cellimm.2011.10.017. PMID 22082567. 
19. “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. (July 2001). doi:10.4049/jimmunol.167.1.311. PMID 11418665. 
20. “Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta”. Biochem. J. 302 (2): 527–34. (September 1994). doi:10.1042/bj3020527. PMC 1137259. PMID 8093006. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1137259/. 
21. “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. (July 1998). doi:10.1006/abbi.1998.0720. PMID 9675033. 
22. “Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity”. J. Biol. Chem. 269 (51): 32634–8. (Dec 1994). doi:10.1016/S0021-9258(18)31681-8. PMID 7798269. 
23. “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. (November 1998). doi:10.1074/jbc.273.47.31455. PMID 9813058. 
24. “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. (August 2000). doi:10.1091/mbc.11.8.2691. PMC 14949. PMID 10930463. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC14949/. 
25. “Determination of type I receptor specificity by the type II receptors for TGF-beta or activin”. Science 262 (5135): 900–2. (November 1993). Bibcode: 1993Sci...262..900E. doi:10.1126/science.8235612. PMID 8235612. 
26. “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. (March 2000). Bibcode: 2000PNAS...97.2626O. doi:10.1073/pnas.97.6.2626. PMC 15979. PMID 10716993. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15979/. 
27. “Conserved role for 14-3-3epsilon downstream of type I TGFbeta receptors”. FEBS Lett. 490 (1–2): 65–9. (February 2001). doi:10.1016/s0014-5793(01)02133-0. PMID 11172812. 

関連文献

• “Transforming growth factor beta in tissue fibrosis”. N. Engl. J. Med. 331 (19): 1286–92. (1994). doi:10.1056/NEJM199411103311907. PMID 7935686. 
• “Latent transforming growth factor-beta: structural features and mechanisms of activation”. Kidney Int. 51 (5): 1376–82. (1997). doi:10.1038/ki.1997.188. PMID 9150447. 
• “The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins”. J. Biol. Chem. 274 (27): 18843–6. (1999). doi:10.1074/jbc.274.27.18843. PMID 10383378. 
• “HIV-1 Tat: immunosuppression via TGF-beta1 induction”. Immunol. Today 20 (8): 384–5. (1999). doi:10.1016/S0167-5699(99)01497-8. PMID 10431160. 
• “Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis”. Pharmacogenetics 11 (9): 765–71. (2001). doi:10.1097/00008571-200112000-00004. PMID 11740340. 
• “TGF-β: Receptors, Signaling Pathways and Autoimmunity”. TGF-beta: receptors, signaling pathways and autoimmunity. Current Directions in Autoimmunity. 5. (2002). 62–91. doi:10.1159/000060548. ISBN 978-3-8055-7308-5. PMID 11826761 
• “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. (2002). doi:10.1080/10428190210195. PMID 11908736. 
• “TGF-beta signal transduction and mesangial cell fibrogenesis”. Am. J. Physiol. Renal Physiol. 284 (2): F243–52. (2003). doi:10.1152/ajprenal.00300.2002. PMID 12529270. 
• “Epithelial-mesenchymal transition and its implications for fibrosis”. J. Clin. Invest. 112 (12): 1776–84. (2003). doi:10.1172/JCI20530. PMC 297008. PMID 14679171. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC297008/. 
• “Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis”. Arterioscler. Thromb. Vasc. Biol. 24 (3): 399–404. (2004). doi:10.1161/01.ATV.0000114567.76772.33. PMID 14699019. 
• “TGFbeta and Wnt pathway cross-talk”. Cancer Metastasis Rev. 23 (1–2): 53–61. (2004). doi:10.1023/A:1025811012690. PMID 15000149. 
• “Transforming growth factor-beta: a clinical target for the treatment of diabetic nephropathy”. Curr. Diab. Rep. 4 (6): 447–54. (2004). doi:10.1007/s11892-004-0055-z. PMID 15539010. 
• “Integrin-mediated activation of latent transforming growth factor beta”. Cancer Metastasis Rev. 24 (3): 395–402. (2005). doi:10.1007/s10555-005-5131-6. PMID 16258727. 
• “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. (2006). doi:10.1111/j.1582-4934.2006.tb00292.x. PMC 3933103. PMID 16563223. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933103/. 
• “Escaping from the TGFbeta anti-proliferative control”. Carcinogenesis 27 (11): 2148–56. (2006). doi:10.1093/carcin/bgl068. PMID 16698802. 
• “Transgenic modeling of transforming growth factor-beta(1): role of apoptosis in fibrosis and alveolar remodeling”. Proc Am Thorac Soc 3 (5): 418–23. (2006). doi:10.1513/pats.200602-017AW. PMC 2658706. PMID 16799085. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658706/. 
• “Transforming growth factor-beta: innately bipolar”. Curr. Opin. Immunol. 19 (1): 55–62. (2007). doi:10.1016/j.coi.2006.11.008. PMID 17137775. https://zenodo.org/record/1258845. 
• “TGF-beta1: a novel target for cardiovascular pharmacology”. Cytokine Growth Factor Rev. 18 (3–4): 279–86. (2007). doi:10.1016/j.cytogfr.2007.04.005. PMID 17485238. 
• “Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update”. J Cereb Blood Flow Metab 40 (9): 1752–1768. (May 2020). doi:10.1177/0271678X20923551. PMC 7446569. PMID 32423330. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446569/. 

外部リンク

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