Inhibition of glycogen synthase (casein) kinase-1 by heparin

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Previous reports have shown that heparin is an inhibitor of casein kinase-2 (CK-2). It is unclear whether heparin is also an inhibitor of glycogen synthase (casein) kinase-1 (CK-1), a type 1 casein kinase. In this study it is shown that CK-1 is potently inhibited by heparin when phosvitin or calcineurin are used as substrates. With casein as a substrate, however, the kinase is insensitive to inhibition by heparin. Using phosvitin as a substrate half-maximal inhibition of CK-1 was observed with 0.14 μg/ml heparin. Kinetic analyses indicate that at a constant concentration (0.10 m m) of ATP the K m of CK-1 for phosvitin is increased eightfold in the presence of 0.9 μg/ml heparin; the V max is unchanged with or without heparin. At a constant concentration of phosvitin (4 mg/ml) heparin (0.9 μg/ml) decreased the V max for ATP by 57%; the K m is unchanged with or without heparin. The inhibition of CK-1 by heparin can be reversed by KCl (>100 m m). These results indicate that heparin is a potent inhibitor not only of CK-2 but also of CK-1. Hence heparin inhibition can no longer be arbitrarily used as a criterion to discriminate between these kinases.