ANNEXIN-I INHIBITS PHOSPHOLIPASE A(2) BY SPECIFIC INTERACTION, NOT BYSUBSTRATE DEPLETION

Annexin-I is a calcium dependent phospholipid binding and phospholipas e A(2) (PLA(2)) inhibitory protein. A 'substrate depletion' model has been proposed for the mechanism of PLA, inhibition by annexin-I in stu dies with 14 to 18 kDa PLA(2)s. Herein, we have studied the inhibition mechanism using 100 kDa cytosolic PLA(2) from porcine spleen. The inh ibition has been measured at various substrate and calcium ion concent rations. The pattern of PLA(2) inhibition by annexin-I was consistent with a 'specific interaction' mechanism rather than the 'substrate dep letion' model. Apparent contradiction with previous studies can be exp lained by the calcium-dependent binding of annexin-I to the substrate.