PT  - JOURNAL ARTICLE
AU  - T Tanaka
AU  - T Ohmura
AU  - T Yamakado
AU  - H Hidaka
TI  - Two types of calcium-dependent protein phosphorylations modulated by calmodulin antagonists. Naphthalenesulfonamide derivatives.
DP  - 1982 Sep 01
TA  - Molecular Pharmacology
PG  - 408--412
VI  - 22
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/22/2/408.short
4100  - http://molpharm.aspetjournals.org/content/22/2/408.full
SO  - Mol Pharmacol1982 Sep 01; 22
AB  - Ca2-dependent protein phosphorylations activated by calmodulin 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 these agents was mediated through a competitive inhibition of enzyme activation by interaction with calmodulin or phospholipid, and Ki values of W-7 for calmodulin-dependent phosphorylation and phospholipid-dependent protein kinase were 12 microM and 110 microM, 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 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. These results suggest that naphthalenesulfonamide derivatives may be more selective inhibitors of Ca2+, calmodulin-dependent protein phosphorylation than is Ca2+-activated, phospholipid-dependent protein kinase and that the mechanism of interaction between W-7 and phosphatidylserine differs from the interaction between W-7 and calmodulin. These agents are useful tools for elucidating the physiological role of Ca2+-dependent protein phosphorylation.