Fig. 11. Schematic depiction of the proposed mechanism for C1P-mediated regulation of cPLA₂α activity in wound repair.

(A) Under normal conditions, an inflammatory stimulus (for example, proinflammatory cytokines or mechanical trauma) initiates a signal cascade (1) that leads to the activation of cPLA₂α and its translocation to intracellular membranes, such as the Golgi apparatus, where it binds to C1P (2). There, cPLA₂α preferentially cleaves arachidonic acid–containing phospholipids at the sn-2 position, releasing free fatty acids (3). Free arachidonic acid can be converted by intracellular enzymes such as COX-1 and COX-2 (4) into PGE₂ through a multi-step process (5). (B) When cPLA₂α cannot bind to C1P, agonist-mediated signaling (1) leads to the activation of cPLA₂α and its translocation to intracellular lipid droplets, where it binds to PIP₂ (2). There, cPLA₂α preferentially cleaves arachidonic acid–containing phospholipids, releasing free fatty acids (3). Free arachidonic acid binds to 5-LO (4), which interacts with FLAP at lipid droplets (4) instead of at the nucleus. FLAP-mediated activation of 5-LO enzymatic activity stimulates the production of 5-HETE, leading to a 5-HETE–dominated eicosanoid profile.