2 TYPES OF CALCIUM-DEPENDENT PROTEIN PHOSPHORYLATIONS MODULATED BY CALMODULIN ANTAGONISTS - NAPHTHALENESULFONAMIDE DERIVATIVES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 22  (2) , 408-412
Abstract
Ca2+-dependent protein phosphorylations activated by [bovine brain] calmoduin or phospholipid were studied using selective inhibitors. Both protein phosphorylations were inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives. Kinetic analysis indicated that the primary effect of those agents was mediated through a competitive inhibition of enzyme activation by interaction with calmodulin or phospholipid, and Ki [inhibition constant] values of W-7 for calmodulin-dependent phosphorylation and phospholipid-dependent protein kinase were 12 .mu.M and 110 .mu.M, respectively. The addition of Ca2+ inhibited the binding of [3H]W-7 to phosphatidylserine but not the binding to calmodulin. The potencies of naphthalenesulfonamide derivatives as inhibitors of Ca2+, calmodulin-dependent protein kinase were dependent on the length of the alkyl chain (C2-C10) but not on Ca2+-activated, phospholipid-dependent protein kinase. Naphthalenesulfonamide derivatives may be more selective inhibitors of Ca2+, calmodulin-dependent protein phosphorylation than is Ca2+-activated, phospholipid-dependent protein kinase and the mechanism of interaction between W-7 and phosphatidylserine apparently differ from the interaction between W-7 and calmodulin. These agents are useful tools for elucidating the physiological role of Ca2+-dependent protein phosphorylation.