Differential effects of annexins I, II, III, and V on cytosolic phospholipase A2 activity: specific interaction model

Annexins (ANXs) are a family of proteins with calcium-dependent phospholipid binding properties, Although inhibition of phospholipase A2 (PLA2) by ANX-I has been reported, the mechanism is still controversial. Previously we proposed a 'specific interaction' model for the mechanism of cytosolic PLA2 (cPLA2) inhibition by ANX-I [Kim et al., FEES Lett. 343 (1993) 251-255]. Here we have studied the cPLA2 inhibition mechanism using ANX-I, N-terminally deleted ANX-I (Delta ANX-I), ANX-II, ANX-II(2)P11(2), ANX-III, and ANX-V. Under the conditions for the specific interaction model, ANX-I, Delta ANX-I, and ANX-II(2)P11(2) inhibited cPLA2, whereas inhibition by ANX-II and ANX-III was negligible, Inhibition by ANX-V was much smaller than that by ANX-I. The protein-protein interactions between cPLA2 and ANX-I, Delta ANX-I, and ANXII(2)P11(2) were verified by immunoprecipitation. We can therefore conclude that inhibition of cPLA2 by specific interaction is not a general function of all ANXs, and is rather a specific function of ANX-I. The results are consistent with the specific interaction model. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.