Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization.
Proc Natl Acad Sci U S A
; 118(32)2021 08 10.
Article
in En
| MEDLINE
| ID: mdl-34349020
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Serine Endopeptidases
/
Extracellular Matrix Proteins
/
Proprotein Convertases
/
Casein Kinase I
Limits:
Animals
/
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2021
Type:
Article
Affiliation country:
China