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Transforming growth factor beta (TGF-β) is a secreted protein that controls proliferation, cellular differentiation, and other functions in most cells. It is a type of cytokine which plays a role in immunity, cancer, bronchial asthma, lung fibrosis, heart disease, diabetes, Hereditary hemorrhagic telangiectasia, Marfan syndrome, Vascular Ehlers-Danlos syndrome,〔http://circ.ahajournals.org/cgi/content/meeting_abstract/120/18_MeetingAbstracts/S1048-b〕 Loeys–Dietz syndrome, Parkinson's disease, Chronic kidney disease,〔https://www.fightaging.org/archives/2014/12/a-novel-approach-to-chronic-kidney-disease.php〕 Multiple Sclerosis and AIDS. TGF-β is secreted by many cell types, including macrophages, in a latent form in which it is complexed with two other polypeptides, latent TGF-beta binding protein (LTBP) and latency-associated peptide (LAP). Serum proteinases such as plasmin catalyze the release of active TGF-β from the complex. This often occurs on the surface of macrophages where the latent TGF-β complex is bound to CD36 via its ligand, thrombospondin-1 (TSP-1). Inflammatory stimuli that activate macrophages enhance the release of active TGF-β by promoting the activation of plasmin. Macrophages can also endocytose IgG-bound latent TGF-β complexes that are secreted by plasma cells and then release active TGF-β into the extracellular fluid.〔(AfCS signaling gateway - data center - ligand description )〕 TGF-β exists in at least three isoforms called TGF-β1, TGF-β2 and TGF-β3. Until the three isoforms were discovered, TGF-β referred to TGF-β1, as it was the first member of this family to be discovered. The TGF-β family is part of a superfamily of proteins known as the transforming growth factor beta superfamily, which includes inhibins, activin, anti-müllerian hormone, bone morphogenetic protein, decapentaplegic and Vg-1. Most tissues have high expression of the genes encoding TGF-β. In contrast, other anti-inflammatory cytokines such as IL-10 show minimal expression in unstimulated tissues and seem to require triggering by commensal or pathogenic flora. TGF-β acts as an antiproliferative factor in normal epithelial cells and at early stages of oncogenesis. Some cells that secrete TGF-β also have receptors for TGF-β. This is known as autocrine signalling. Cancerous cells increase their production of TGF-β, which also acts on surrounding cells. ==Structure== The peptide structures of the TGF-β isoforms are highly similar (homologies on the order of 70-80 %). They are all encoded as large protein precursors; TGF-β1 contains 390 amino acids and TGF-β2 and TGF-β3 each contain 412 amino acids. They each have an N-terminal signal peptide of 20-30 amino acids that they require for secretion from a cell, a pro-region (called latency associated peptide or LAP), and a 112-114 amino acid C-terminal region that becomes the ''mature'' TGF-β molecule following its release from the pro-region by proteolytic cleavage. The mature TGF-β protein dimerizes to produce a 25 KDa active protein with many conserved structural motifs. TGF-β has nine cysteine residues that are conserved among its family. Eight form disulfide bonds within the protein to create a cysteine knot structure characteristic of the TGF-β superfamily. While, the ninth cysteine forms a disulfide bond with the ninth cysteine of another TGF-β protein to produce a dimer. Many other conserved residues in TGF-β are thought to form secondary structure through hydrophobic interactions. The region between the fifth and sixth conserved cysteines houses the most divergent area of TGF-β proteins that is exposed at the surface of the protein and is implicated in receptor binding and specificity of TGF-β. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Transforming growth factor beta」の詳細全文を読む スポンサード リンク
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