TGF-β:: from latent to active
TGF-β:: from latent to active
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DOI：
10.1016/s1286-4579(99)00259-2
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发表时间：
1999-12-01
影响因子：
5.8
通讯作者：
Khalil, N
中科院分区：
文献类型：
--
作者：
Khalil, N
转化生长因子- β (tgf - β s)作为前体蛋白合成，在分泌前在细胞内修饰。最相关的细胞内修饰之一是从蛋白质的n端部分切割c端前区。c端前区被称为潜伏期相关肽（LAP），而n端区域被称为成熟tgf - β或活性tgf - β。然而，除了一些例外，LAP在分泌前与成熟的tgf - β非共价结合。当成熟的tgf - β与LAP相关时，它被称为l - tgf - β，它不能与其受体相互作用，也没有生物学效应。tgf - β s及其受体的表达非常普遍，这表明tgf - β活性的调控可能是复杂的、多因素的。然而，控制tgf - β 3生物效应的最重要手段之一是调节l - tgf - β转化为活性tgf - β。目前的文献支持l - tgf - β的两种主要激活机制，并表明l - tgf - β的激活机制可能是多种多样的，并且依赖于环境。为了使tgf - β具有生物活性，必须将LAP从与l - tgf - β的关联中释放出来，或者进行构象改变，使LAP不从l - tgf - β复合物中释放出来，而是暴露tgf - β受体结合位点。由于tgf - β与许多疾病的发病机制有关，因此在这种情况下，l - tgf - β激活的各种机制提供了控制tgf - β活性的可能性，该活性局限于受感器官和更具体的疾病过程。(C) 1999年版科学与医学爱思唯尔。
The transforming growth factor-betas (TGF-beta s) are synthesized as precursor proteins that are modified intracellularly prior to secretion. One of che most relevant intracellular modifications is the cleavage of the C-terminal pro-region from the N-terminal portion of the protein. The C-terminal pro-region is referred to as the latency-associated peptide (LAP) while the N-terminal region is called the mature TGF-beta or active TGF-beta. However, with some exceptions the LAP noncovalently associates with the mature TGF-beta prior to secretion. When the mature TGF-beta is associated with the LAP it is called L-TGF-beta and cannot interact with its receptor and has no biological effect. The TGF-beta s and their receptors are very ubiquitously expressed, suggesting that the regulation of TGF-beta activity is likely to be complex and multifactorial. However, one of che most important means of controlling the biological effects of TGF-beta 3 is the regulation of converting L-TGF-beta to active TGF-beta. The current literature supports two major mechanisms of activation of L-TGF-beta and suggests that the mechanism of activation of L-TGF-beta may be varied and context-dependent. For TGF-beta to become biologically active the LAP has to be either released from its associations with L-TGF-beta or undergo conformational change such that the LAP is not released from the L-TGF-beta complex but exposes the TGF-beta receptor binding site. Since TGF-beta has been associated with the pathogenesis of numerous diseases, the various mechanisms of activation of L-TGF-beta in context offer the possibility of controlling TGF-beta activity localized to the organ of involvement and to a more specific disease process. (C) 1999 Editions scientifiques et medicales Elsevier.