Regulatory and functional compartment of three multifunctional protein kinase systems.
Cyclic AMP-dependent protein kinase has been well established to be composed of catalytic and regulatory subunits, and cyclic AMP acts to dissociate these subunits to exhibit full enzymatic activity. In contrast, cyclic GMP-dependent protein kinase does not possess such a subunit structure and is activated by cyclic GMP simply in an allosteric manner. In addition to cyclic AMP-dependent and cyclic GMP-dependent protein kinases, another species of multifunctional protein kinase has been found in many mammalian tissues. This protein kinase is entirely independent of cyclic nucleotides and activated by lower concentrations of Ca2+ in the presence of a membrane-associated factor. This factor has been identified as phospholipids; in fact, phosphatidylinositol and phosphatidylserine are active in this role, whereas lecithin and sphingomyelin are unable to activate the enzyme. Thus, the three species of protein kinases mentioned above are activated in different manners. Nevertheless, these enzymes show very similar substrate specificities and phosphorylate the same specific seryl residues of histone fractions. In addition, all enzymes have abilities to activate and inactivate muscle phosphorylase kinase and glycogen synthetase, respectively, although the relative rates of reactions towards various substrates are markedly different. The Ca2+-dependent protein kinase seems to be associated with membranous components, whereas cyclic GMP-dependent protein kinase appears to be related to certain subcellular organella such as nucleus. Suggestive evidence is available implying that the cyclic AMP-, cyclic GMP- and Ca2+-activated three sets of protein kinase systems may play each specific physiological roles presumably owing to their own subcellular compartments.
D002118:Calcium / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006006:Glycogen Synthase / Q000378:metabolism; D007700:Kinetics; D010764:Phosphorylase Kinase / Q000378:metabolism; D006656:Protamine Kinase / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013379:Substrate Specificity
D000242:Cyclic AMP; D006006:Glycogen Synthase; D011494:Protein Kinases; D010764:Phosphorylase Kinase; D006656:Protamine Kinase; D006152:Cyclic GMP; D002118:Calcium