Golgi stress response by proteoglycans

糖胺聚糖（Glycosaminoglycans，GAG）是蛋白聚糖（proteoglycans，PG）的组成部分，其在大多数细胞的表面和细胞外基质中丰富。已知PG在多种生物过程中作为辅因子起作用。PG的大多数生物活性归因于GAG侧链，其通过特定的糖序列与不同的蛋白质配体相互作用。EXTL2是肿瘤抑制因子EXT家族的成员，其功能是抑制由木糖激酶增强的任何GAG生物合成，因此缺乏EXTL2会导致GAG过度产生和GAG的结构变化。这些低质量的糖胺酸对细胞信号传导如HGF介导的和BMP介导的信号传导有影响，从而干扰肝再生和血管重塑。因此，调节GAG生物合成的EXTL2依赖性机制可能是PG的“质量控制系统”，并且在不存在EXTL2的情况下产生的GAG可能与疾病密切相关。

Glycosaminoglycans (GAGs) are components of proteoglycans (PGs), which are abundant on the surfaces of most cells and in extracellular matrices. PGs are known to function as cofactors in a variety of biological processes. Most biological activities of PGs are attributed to the GAG side chains that interact with diverse protein ligands via specific saccharide sequences. EXTL2, a member of the EXT family of tumor suppressors, functions to suppress any GAG biosynthesis that is enhanced by a xylose kinase, and thus lack of EXTL2 causes GAG overproduction and structural changes to GAGs. These poor-quality GAGs have effects on the cell signaling such as HGF-mediated and BMP-mediated signaling, and consequently disturb liver regeneration and blood vessel remodeling. Therefore, the EXTL2-dependent mechanism that regulates GAG biosynthesis might be a "quality control system" for PGs and GAGs produced in the absence of EXTL2 can be closely associated with diseases.