klotho是α-、β-和γ-分泌酶的底物。
Klotho is a substrate for alpha-, beta- and gamma-secretase.
作者信息
Bloch Laura, Sineshchekova Olga, Reichenbach Daniela, Reiss Karina, Saftig Paul, Kuro-o Makoto, Kaether Christoph
机构信息
Leibniz Institut für Altersforschung-Fritz Lipmann Institut, Beutenbergstr. 11, 07745 Jena, Germany.
出版信息
FEBS Lett. 2009 Oct 6;583(19):3221-4. doi: 10.1016/j.febslet.2009.09.009. Epub 2009 Sep 6.
Abstract
Klotho is an anti-aging protein with different functions of the full-length membrane protein and the secreted hormone-like form. Using overexpression and knock-down approaches as well as embryonic fibroblasts of knock-out mice we present evidence that Klotho is shedded by the alpha-secretases ADAM10 and 17 as well as by the beta-secretase beta-APP cleaving enzyme 1. The remaining membrane-bound fragment is a substrate for regulated intramembrane proteolysis by gamma-secretase. Our data suggest that therapeutic approaches targeting these proteases should be carefully analyzed for potential side effects on Klotho-mediated physiological processes.
摘要
α-klotho是一种具有抗衰老功能的蛋白质，全长膜蛋白和分泌的激素样形式具有不同的功能。我们使用过表达和敲低方法以及基因敲除小鼠的胚胎成纤维细胞，证明α-klotho可被α-分泌酶ADAM10和ADAM17以及β-分泌酶β-淀粉样前体蛋白裂解酶1切割。剩余的膜结合片段是γ-分泌酶介导的调节性膜内蛋白水解的底物。我们的数据表明，针对这些蛋白酶的治疗方法应仔细分析其对α-klotho介导的生理过程的潜在副作用。
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ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor alpha, L-selectin, and tumor necrosis factor alpha.ADAMs 10和17代表了一种用于膜蛋白（如转化生长因子α、L-选择素和肿瘤坏死因子α）的通用脱落机制中受不同调节的成分。
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Klotho converts canonical FGF receptor into a specific receptor for FGF23.α-klotho将经典成纤维细胞生长因子受体转化为成纤维细胞生长因子23的特异性受体。
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Regulation of fibroblast growth factor-23 signaling by klotho.α-klotho对成纤维细胞生长因子23信号的调节作用
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