一种用于半胱氨酸去棕榈酰化的荧光探针揭示了动态的 APT 信号传导。

Kathayat Rahul S, Elvira Pablo D, Dickinson Bryan C

Department of Chemistry, University of Chicago, Chicago, Illinois, USA.

Nat Chem Biol. 2017 Feb;13(2):150-152. doi: 10.1038/nchembio.2262. Epub 2016 Dec 19.

Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoylation, acylprotein thioesterases (APTs). Live-cell analysis with DPPs reveals rapid growth-factor-mediated inhibition of the depalmitoylation activity of APTs, exposing a novel regulatory mechanism of dynamic lipid signaling.

数百种人类蛋白质通过半胱氨酸残基的可逆棕榈酰化（S-棕榈酰化）进行修饰，但对去棕榈酰化的调控却知之甚少。在这里，我们开发了“去棕榈酰化探针”（DPPs），即小分子荧光团，以监测S-棕榈酰化“擦除器”——酰基蛋白硫酯酶（APTs）的内源性活性水平。使用DPPs进行的活细胞分析揭示了生长因子对APTs去棕榈酰化活性的快速介导抑制作用，从而揭示了一种动态脂质信号传导的新型调控机制。