Identification of a novel post-translational modification of epidermal growth factor domains and mechanistic analysis of the modification

表皮生长因子（EGF）结构域用独特的O-连接聚糖进行后修饰。EGF结构域上的O-聚糖的经典类型是O-岩藻糖和O-葡萄糖聚糖，在许多血浆糖蛋白和信号分子上发现，其生物学功能已被证明，特别是在Notch信号通路的背景下。在这项研究中，我们发现O-GlcNAc修饰作为一种新的修饰的EGF结构域上发生的保守的Ser/Thr残基位于第五和第六半胱氨酸残基之间的Notch受体的EGF结构域在果蝇。此外，我们已经成功地分离出一个新的基因，Eogt，负责细胞外O-GlcNAc化。对Eogt生理功能的研究将揭示O-GlcNAc酰化在细胞外环境中的新的生物学作用。

Epidermal growth factor (EGF) domains are posttranslationally modified with unique O-linked glycans. The classical types of O-glycans on EGF domains are O-fucose and O-glucose glycans, found on many plasma glycoproteins and signaling molecules, whose biological functions have been demonstrated especially in the context of the Notch signaling pathway. In this study, we have discovered O-GlcNAc modification as a new modification of the EGF domain that occurs on the conserved Ser/Thr residue located between the fifth and sixth cysteine residues within the EGF domains of Notch receptors in Drosophila. Moreover, we have succeeded in the isolation of a new gene, Eogt, responsible for the extracellular O-GlcNAcylation. Characterization of physiological function of Eogt will reveal the new biological roles for O-GlcNAcylation in the extracellular environment.