Mechanism of activation of cyclic GMP-dependent protein kinase from rat liver by multiple modulators.
A number of polyanionic compounds, including DNA, RNA and polyglutamate, were shown to exhibit protein kinase stimulatory modulator activity as they were required for cyclic GMP to stimulate the phosphorylation of various cationic substrates by rat liver cyclic GMP-dependent protein kinase. Anionic proteins (casein, phosvitin) were phosphorylated poorly by the enzyme and their phosphorylation was not stimulated by the stimulatory modulators. Studies of the mechanism of action suggest that the modulators interact directly with the substrates to form a complex which is a better substrate than free histone. The observed effect of modulator is complex as it depends on the ratio of modulator to histone and the resultant state of the complex formed (better or poorer substrate than free histone). The observed effect is also dependent on the properties of the histone substrate as Michaelis-Menten kinetics are not observed in the phosphorylation of arginine-rich histone in the absence or presence of cyclic GMP.
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D004247:DNA / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D011099:Polyglutamic Acid / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism* / Q000494:pharmacology*; D012313:RNA / Q000494:pharmacology; D051381:Rats; D013379:Substrate Specificity
D002352:Carrier Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; D011099:Polyglutamic Acid; D012313:RNA; D004247:DNA; D011494:Protein Kinases; D008274:Magnesium