INSERM U781, Paris, France.
J Invest Dermatol. 2011 Nov;131(11):2169-73. doi: 10.1038/jid.2011.295.
Lymphoepithelial Kazal-type related inhibitor (LEKTI) is a multidomain proteinase inhibitor whose defective expression causes Netherton syndrome (NS). LEKTI is encoded by SPINK5, which is also a susceptibility gene for atopic disease. In this issue, Fortugno et al. report an elegant and thorough study of the LEKTI proteolytic activation process in which they identify the precise nature of the cleavage sites used and the bioactive fragments generated. They propose a proteolytic activation model in human skin and confirm differential inhibition of kallikrein (KLK) 5, 7, and 14 by the major physiological LEKTI fragments. They show that these bioactive fragments inhibit KLK-mediated proteolysis of desmoglein 1 (DSG1) and suggest a fine-tuned inhibition process controlling target serine proteinase (SP) activity.
淋巴上皮 Kazal 型相关抑制剂 (LEKTI) 是一种多功能蛋白酶抑制剂，其表达缺陷会导致 Netherton 综合征 (NS)。LEKTI 由 SPINK5 编码，SPINK5 也是特应性疾病的易感基因。在本期杂志中，Fortugno 等人报告了一项关于 LEKTI 蛋白水解激活过程的优雅而彻底的研究，他们确定了所使用的切割位点的精确性质以及产生的生物活性片段。他们提出了一个人皮肤中的蛋白水解激活模型，并证实了主要的生理 LEKTI 片段对激肽释放酶 (KLK)5、7 和 14 的差异抑制作用。他们表明这些生物活性片段抑制 KLK 介导的桥粒芯糖蛋白 1 (DSG1)的蛋白水解，并提出了一个精细的抑制过程来控制靶丝氨酸蛋白酶 (SP) 的活性。
