Thrombin activation of protein C requires prior processing by a liver proprotein convertase.

ABSTRACT: Protein C, a secretory vitamin K-dependent anticoagulant serine protease, inactivates factors Va/VIIIa. It is exclusively synthesized in liver hepatocytes as an inactive zymogen (proprotein C). In humans, thrombin cleavage of the propeptide at PR²²¹↓ results in activated protein C (APC; residues 222-461). However, the propeptide is also cleaved by a furin-like proprotein convertase(s) (PCs) at KKRSHLKR¹⁹⁹↓ (underlined basic residues critical for the recognition by PCs), but the order of cleavage is unknown. Herein, we present evidence that at the surface of COS-1 cells, mouse proprotein C is first cleaved by the convertases furin, PC5/6A, and PACE4. In mice, this cleavage occurs at the equivalent site, KKRKILKR¹⁹⁸↓,

SUBMITTER: Essalmani R 

PROVIDER: S-EPMC5481563 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature