Effects of adenosine and its derivatives on protein kinase activity of beef thyroid

Effects of adenosine and some of its derivatives on beef protein kinase activity were investigated in vitro. Adenosine rapidly inhibited protein kinase activity in a dose-dependent manner. Significant inhibition occured with 10 μM and half-maximal inhibition at 100 μM adenosine. Inhibition was almost complete with 5 mM adenosine. Inhibition was similar whether protein kinase activity was assayed with or without cyclic AMP. The inhibition by adenosine was reversed by increasing the concentration of ATP and Lineweaver-Burk analysis indicated that adenosine inhibition was competitive with ATP. Addition of adenosine deaminase to the incubation medium prevented the inhibition induced by adenosine. Intact 1 and N⁶ positions of adenosine were important for the inhibition since their mondification was associated with loss of inhibition. Modification of the 8 position of adenosine decreased, but did not abolish, the inhibition. The 2 and 3 position of ribose did not seem to be critical since 2- and 3-deoxyadenosine produced inhibition similar to that of adenosine.