Kitabgi Patrick
INSERM U732, Université Pierre et Marie Curie, Hopital St. Antoine, 184 rue du Faubourg St. Antoine, 75571 Paris Cedex 12, France.
Peptides. 2006 Oct;27(10):2508-14. doi: 10.1016/j.peptides.2006.03.038. Epub 2006 Aug 9.
Neurotensin (NT) is synthesized as part of a larger precursor that also contains neuromedin N (NN), a six amino acid neurotensin-like peptide. NT and NN are located in the C-terminal region of the precursor (pro-NT/NN) where they are flanked and separated by three Lys-Arg sequences. A fourth dibasic sequence is present in the middle of the precursor. Dibasics are the consensus sites recognized and cleaved by endoproteases that belong to the recently identified family of pro-protein convertases (PCs). In tissues that express pro-NT/NN, the three C-terminal Lys-Arg sites are differentially processed, whereas the middle dibasic is poorly cleaved. Pro-NT/NN processing gives rise mainly to NT and NN in the brain, to NT and a large peptide ending with the NN sequence at its C-terminus (large NN) in the gut and to NT, large NN and a large peptide ending with the NT sequence (large NT) in the adrenals. Recent evidence indicates that PC1, PC2 and PC5-A are the pro-hormone convertases responsible for the processing patterns observed in the gut, brain and adrenals, respectively. As NT, NN, large NT and large NN are all endowed with biological activity, the evidence reviewed here supports the idea that post-translational processing of pro-NT/NN in tissues may generate biological diversity.
神经降压素（NT）作为一种较大前体的一部分被合成，该前体还包含神经介素N（NN），一种由六个氨基酸组成的神经降压素样肽。NT和NN位于前体（前神经降压素/神经介素N，pro-NT/NN）的C末端区域，它们两侧由三个赖氨酸-精氨酸（Lys-Arg）序列隔开。第四个双碱性序列存在于前体中间。双碱性序列是属于最近鉴定的前体蛋白转化酶（PCs）家族的内切蛋白酶识别并切割的共有位点。在表达pro-NT/NN的组织中，三个C末端的Lys-Arg位点的加工方式不同，而中间的双碱性序列切割较少。pro-NT/NN的加工在大脑中主要产生NT和NN，在肠道中产生NT和一种在其C末端以NN序列结尾的大肽（大NN），在肾上腺中产生NT、大NN和一种以NT序列结尾的大肽（大NT）。最近的证据表明，PC1、PC2和PC5-A分别是负责在肠道、大脑和肾上腺中观察到的加工模式的前激素转化酶。由于NT、NN、大NT和大NN都具有生物活性，这里综述的证据支持这样一种观点，即组织中pro-NT/NN的翻译后加工可能产生生物多样性。
