Independent regulation of pyruvate kinase expression by cyclic AMP and prostaglandin F 2α in mouse mastocytoma cells

Abstract

P-815 mouse mastocytoma cells express the K isozyme of pyruvate kinase and the specific activity of this enzyme is increased in response to N 6 ,2′- O-dibutyryladenosine 3′:5′-cyclic monophosphate, 8-bromoadenosine 3′:5′-cyclic monophosphate, cholera toxin, and epinephrine, all of which also elevate the intracellular concentration of adenosine 3′:5′-cyclic monophosphate. Prostaglandin F 2α also increases the cellular activity of this enzyme, but does not increase the adenosine 3′:5′-cyclic monophosphate levels. Under all these conditions, the increase in enzymatic activity is accompanied by an equivalent increase in the pyruvate kinase protein level. However, neither the rate of enzyme synthesis nor the level of pyruvate kinase mRNA is elevated by N 6 ,2′- O-dibutyryladenosine 3′:5′-cyclic monophosphate. On the other hand, it does increase the enzyme's half-life. In contrast, prostaglandin F 2α increases the rate of synthesis and the level of pyruvate kinase K mRNA, but has no influence on the rate of degradation. Therefore, these cells have two mechanisms which increase pyruvate kinase K levels. One operates via an increase in cAMP level and results in a decrease in the rate of degradation, whereas the other minimizes an upsurge in cAMP levels but still increases pyruvate kinase K activity by increasing its rate of synthesis.