分泌物
分泌途径
细胞生物学
高尔基体
跨膜蛋白
蛋白酶
分泌蛋白
化学
激酶
生物
生物化学
酶
内质网
受体
作者
Xinxin Chen,J. Zhang,Pulan Liu,Yu‐Sheng Wei,Wang Xie,Junyu Xiao,Chih‐Chen Wang,Lei Wang
标识
DOI:10.1073/pnas.2100133118
摘要
Family with sequence similarity 20C (Fam20C), the major protein kinase in the secretory pathway, generates the vast majority of the secreted phosphoproteome. However, the regulatory mechanisms of Fam20C transport, secretion, and function remain largely unexplored. Here, we show that Fam20C exists as a type II transmembrane protein within the secretory compartments, with its N-terminal signal peptide-like region serving as a membrane anchor for Golgi retention. The secretion and kinase activity of Fam20C are governed by site-1 protease (S1P), a key regulator of cholesterol homeostasis. We find that only mature Fam20C processed by S1P functions in osteoblast differentiation and mineralization. Together, our findings reveal a unique mechanism for Fam20C secretion and activation via proteolytic regulation, providing a molecular link between biomineralization and lipid metabolism.
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