Annexin‐I inhibits phospholipase A2 by specific interaction, not by substrate depletion

Abstract

Annexin-I is a calcium dependent phospholipid binding and phospholipase A₂ (PLA₂) inhibitory protein. A ‘substrate depletion’ model has been proposed for the mechanism of PLA₂ inhibition by annexin-I in studies with 14 to 18 kDa PLA₂s. Herein, we have studied the inhibition mechanism using 100 kDa cytosolic PLA₂ from porcine spleen. The inhibition has been measured at various substrate and calcium ion concentrations. The pattern of PLA₂ inhibition by annexin-I was consistent with a ‘specific interaction’ mechanism rather than the ‘substrate depletion’ model. Apparent contradiction with previous studies can be explained by the calcium-dependent binding of annexin-I to the substrate.