Activity of protein kinase dependent on adenosine 3':5'-monophosphate and of its thermostable protein inhibitor in rat hepatoma (HTC) cells. Unlikely role in the permissive action of glucocorticoids.
Normal expression of a variety of hormonal effects which depend on cyclic AMP (adenosine 3':5'-monophosphate) requires the presence of glucocorticoids. Our hypothesis was that glucocorticoids control directly or indirectly the activity of cyclic-AMP-dependent protein kinase. This has been investigated in cultured hepatoma (HTC) cells in which N6,O2'-dibutyryladenosine 3':5'-monophosphate increases the activity of tyrosine transaminase only after glucocorticoid treatment. In these cells, we have determined the concentration and half-life of protein kinase, the sensitivity of this enzyme in vitro to cyclic AMP and to its thermostable protein inhibitor, the state of dissociation of protein kinase holoenzyme in vivo and its sensitivity, in the intact cell, to dibutyryladenosine 3':5'-monophosphate and to the inhibitor diamide, and we have also determined the concentration of endogenous thermostable protein inhibitor of protein kinase. None of these parameters were influenced by glucocorticoids under conditions where these hormones stimulate the activity of tyrosine transaminase and restore sensitivity to dibutyryladenosine 3':5'-monophosphate. It is concluded that the permissive action of glucocorticoids probably results from a control of cyclic-AMP-dependent processes exerted at a level beyond the protein kinase system.
D003994:Bucladesine / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004355:Drug Stability; D004357:Drug Synergism; D008113:Liver Neoplasms; D009363:Neoplasm Proteins / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000201:enzymology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D013696:Temperature
D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D003994:Bucladesine; D003907:Dexamethasone; D000242:Cyclic AMP; D011494:Protein Kinases