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., FEBS Lett. 343 (1994) 251-255]. Here we have studied the cPLA2 inhibition mechanism using ANX-I, N-terminally deleted ANX-I (DeltaANX-I), ANX-II, ANX-II(2)P11(2), ANX-III, and ANX-V. Under the conditions for the specific interaction model, ANX-I, DeltaANX-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, DeltaANX-I, and ANX-II(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.
Kim
S
S
Department of Biochemistry, College of Medicine, University of Ulsan, South Korea.
Ko
J
J
Kim
J H
JH
Choi
E C
EC
Na
D S
DS
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology; D017306:Annexin A2 / Q000494:pharmacology; D017318:Annexin A3 / Q000494:pharmacology; D017304:Annexin A5 / Q000494:pharmacology; D017302:Annexins / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D010741:Phospholipases A / Q000187:drug effects* / Q000378:metabolism; D054467:Phospholipases A2; D011233:Precipitin Tests
D017305:Annexin A1; D017306:Annexin A2; D017304:Annexin A5; D017302:Annexins; D010741:Phospholipases A; D054467:Phospholipases A2; D017318:Annexin A3; D002118:Calcium