Thrombin-induced reactive oxygen species generation in platelets: A novel role for protease-activated receptor 4 and GPIbα.

Both GPIbα and PAR4 are required for thrombin-induced ROS formation, suggesting a novel functional cooperation between GPIbα and PAR4. (A) Thrombin binds GPIbα, via the sulphated tyrosine sequence, and cleaves PAR4, activating the signalling molecules FAK and NOX1 and generating ROS. B. Nk protease cleaves GPIbα and inhibits thrombin-induced ROS generation, whilst hindering PAR4-induced ROS production. In the presence of the PAR4 antagonist, tcY-NH2, PAR4-AP-induced ROS production is abolished. GP: glycoprotein; PAR: protease activated receptor; FAK: focal adhesion kinase; NOX: NADPH oxidase; ROS: reactive oxygen species; Nk: Naja kouthia; AP: activating peptide.