Inhibition of cyclic AMP-dependent protein kinase by curcumin

Curcumin [diferuloylmethane; 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], a major bioactive secondary metabolite found in the rhizomes of turmeric (Curcuma longa), is an inhibitor of Ca2+ and phospholipid-dependent protein kinase C (PKC) and of the catalytic subunit (cAK) of cyclic AMP-dependent protein kinase (IC50 values 15 and 4.8 mu M, respectively). Curcumin inhibits plant Ca2+-dependent protein kinase (CDPK) (IC50 41 mu M), but does not inhibit myosin light chain kinase or a high affinity 3',5'-cyclic AMP-binding phosphatase. Curcumin inhibits cAK, PKC and CDPK in a fashion that is competitive with respect to both ATP and the synthetic peptide substrate employed. The IC50 values for inhibition of cAK by curcumin are very similar when measured with kemptide (LRRASLG) (in the presence or absence of ovalbumin) or with casein or histone III-S as substrates. However, the presence of bovine serum albumin (0.8 mg ml(-1)) largely overcomes inhibition of cAK by curcumin.