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Molecular Pharmacology

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Abstract

Two types of calcium-dependent protein phosphorylations modulated by calmodulin antagonists. Naphthalenesulfonamide derivatives.

T Tanaka, T Ohmura, T Yamakado and H Hidaka
Molecular Pharmacology September 1982, 22 (2) 408-412;
T Tanaka
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T Ohmura
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T Yamakado
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H Hidaka
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Abstract

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.

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Molecular Pharmacology
Vol. 22, Issue 2
1 Sep 1982
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Abstract

Two types of calcium-dependent protein phosphorylations modulated by calmodulin antagonists. Naphthalenesulfonamide derivatives.

T Tanaka, T Ohmura, T Yamakado and H Hidaka
Molecular Pharmacology September 1, 1982, 22 (2) 408-412;

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Abstract

Two types of calcium-dependent protein phosphorylations modulated by calmodulin antagonists. Naphthalenesulfonamide derivatives.

T Tanaka, T Ohmura, T Yamakado and H Hidaka
Molecular Pharmacology September 1, 1982, 22 (2) 408-412;
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