Suppressed ORAI1-STIM1-dependent Ca²⁺ entry by protein kinase C isoforms regulating platelet procoagulant activity.

ABSTRACT: Agonist-induced rises in cytosolic Ca²⁺ control most platelet responses in thrombosis and hemostasis. In human platelets, we earlier demonstrated that the ORAI1-STIM1 pathway is a major component of extracellular Ca²⁺ entry, in particular when induced via the ITAM-linked collagen receptor, glycoprotein VI (GPVI). In the present article, using functionally defective platelets from patients with a loss-of-function mutation in ORAI1 or STIM1, we show that Ca²⁺ entry induced by the endoplasmic reticulum ATPase inhibitor, thapsigargin, fully relies on this pathway. We demonstrate that both the GPVI-induced and thapsigargin-induced Ca²⁺ entry are strongly suppressed by protein kinase C (PKC) activation while leaving intracellular Ca²⁺ mobili

SUBMITTER: Zou J 

PROVIDER: S-EPMC11742345 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature