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Protease-activated receptor signaling in platelets activates cytosolic phospholipase A2α differently for cyclooxygenase-1 and 12-lipoxygenase catalysis.


Holinstat MMichael , Boutaud O Olivier , Apopa PL Patrick L , Vesci J Joanne , Bala M Manju , Oates JA John A , Hamm HE Heidi E . Arteriosclerosis, thrombosis, and vascular biology. 2011 2 ; 31(2). 435-42


The rate-limiting step in the biosynthesis of thromboxane A(2) (TxA(2)) and 12-hydroxyeicosatetraenoic acid (12-HETE) by platelets is activation of cytosolic phospholipase A(2α) (cPLA(2α)), which releases arachidonic acid, which is the substrate for cyclooxygenase-1 (COX-1) and 12-lipoxygenase. We evaluated signaling via the human platelet thrombin receptors, protease-activated receptor (PAR) 1 and PAR4, to the activation of cPLA(2α), which provides a substrate for the biosynthesis of TxA(2) and 12-HETE.