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 contraction with previous studies can be explained by the calcium-dependent binding of annexin-I to the substrate.