Work

Structural determinants of protease-activated receptor 1 cleavage by activated protein C

Year: 2025

Type: article

Abstract: BACKGROUND: Activated protein C (APC) performs cytoprotective functions mediated by cleavage of the protease-activated receptor 1 (PAR1) in the presence of the endothelial protein C receptor and signaling through β-arrestin-2. APC cleaves PAR1 at R41 and R46, but the specificity of the reaction is low. In contrast, thrombin cleaves PAR1 at R41 only in a reaction that is independent of endothelial protein C receptor, producing a proinflammatory response mediated by signaling through G-protein intermediates and features high specificity. The molecular basis of this difference between APC and thrombin remains unknown. OBJECTIVES: To identify the structural determinants of APC that influence PAR1 specificity. METHODS: ). RESULTS: also showed significantly reduced activity toward factor Va. CONCLUSION: The 37, 60, and 99 segments of APC determine the cytoprotective and anticoagulant properties of the enzyme.

Source: Journal of Thrombosis and Haemostasis

DOI: 10.1016/j.jtha.2025.05.034

Authors: Bosko M. Stojanovski, Enrico Di Cera

Institution: Saint Louis University

Language: English

Topic: Blood Coagulation and Thrombosis Mechanisms

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,750