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.