Membrane targeting of palmitoylated Wnt and Hedgehog revealed by chemical probes
Membrane targeting of palmitoylated Wnt and Hedgehog revealed by chemical probes
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DOI：
10.1016/j.febslet.2011.06.033
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发表时间：
2011-08-01
期刊：
影响因子：
3.5
通讯作者：
Hannoush, Rami N.
中科院分区：
文献类型：
--
作者：
Gao, Xinxin;Arenas-Ramirez, Natalia;Hannoush, Rami N.
Wnt和Hedgehog蛋白的棕榈酰化对于维持其生理功能至关重要。迄今为止，还没有报道表征这些蛋白质的棕榈酰化形式的细胞分布的研究。在这里，我们描述了亚细胞定位的棕榈酰化Wnt和Sonic刺猬通过使用一个高度敏感的和非放射性的标记方法，利用炔基棕榈酸。我们发现，棕榈酰化的Wnt和Sonic Hedgehog定位于细胞膜组分，突出了棕榈酰化在这些蛋白质的膜协会的作用。本文所述的方法具有在药物发现中验证Wnt和Hedgehog酰基转移酶的抑制剂的效用，并且能够进一步研究棕榈酰化在这些蛋白质的分泌和信号传导中的作用。(C)2011年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
Palmitoylation of the Wnt and Hedgehog proteins is critical for maintaining their physiological functions. To date, there are no reported studies that characterize the cellular distribution of the palmitoylated forms of these proteins. Here, we describe the subcellular localization of palmitoylated Wnt and Sonic Hedgehog by using a highly sensitive and non-radioactive labeling method that utilizes alkynyl palmitic acid. We show that palmitoylated Wnt and Sonic Hedgehog localize to cellular membrane fractions only, highlighting a role for palmitoylation in the membrane association of these proteins. The method described herein has the utility to validate inhibitors of Wnt and Hedgehog acyltransferases in drug discovery, and enables further investigations of the role of palmitoylation in the secretion and signaling of these proteins. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.