Partial purification of nuclear protein kinases from mouse brain and the effect of chronic morphine treatment

To deduce whether the chronic morphine specific increase in apparent protein kinase activity in chromatin isolated from mouse brain (Oguri et al., 1976) results from a change in nuclear protein kinase enzyme activity or from a property inherent in the phosphoproteins themselves, the nuclear protein kinase from small dense nuclei of mouse brain have been solubilized and partially purified by ammonium sulfate precipitation and phosphocellulose column chromatography. Elution of the phosphocellulose column by a linear NaCl gradient (0 - 1.0 M NaCl) results in one major peak of protein kinase activity when assayed with exogenous casein as substrate. The major peak is cAMP-dependent and two minor peaks eluting at a higher NaCl concentration are cAMP-dependent. Chronic morphine studies indicate an increased specific protein kinase activity. It is not known whether these changes in specific activity are due to alterations in certain properties of the protein kinase(s) or to different isozymes of protein kinase. The significance of these findings will be discussed.