Variation of activity of protein kinases in unstimulated and phytohemagglutinin-stimulated normal and leukemic human lymphocytes.

Cyclic adenosine 3':5'-monophosphate-dependent protein kinase (kinase A) and cyclic guanosine 3':5'-monophosphate-dependent protein kinase (kinase G) were assayed in lymphocytes of normal subjects, adults with chronic lymphocytic leukemia (CLL), and children with acute lymphocytic leukemia (ALL). There was a good correlation between the activity of the two kinases and the level of the corresponding cyclic nucleotides. This was true for cultured phytohemagglutinin-stimulated normal lymphocytes and CLL lymphocytes as well. Kinase A activity was low and kinase G activity was high in leukemic cells in the absence of the respective cyclic nucleotides [5 and 8 units (pmol 32P incorporated into histone per min per mg protein) for kinase A and 98 and 51 units for kinase G in ALL and CLL lymphocytes, respectively]. Upon addition of cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate in vitro, values for kinase A activity returned to normal (approximately 30 units), whereas those for kinase G increased further (212 units for ALL and 85 units for CLL lymphocytes; 22 units was the kinase activity for normal lymphocytes). These findings suggest that cyclic nucleotides achieve thetr specificity in the regulation of the cell, in part, through the activation of the dependent protein kinases and that both kinase A and kinase G may be functionally intact in leukemic cells.