Several factors were found which determine whether the effect of the modulator on protein kinase activity is stimulatory or inhibitory in nature. These include the kind and concentration of substrate protein, the kind and concentration of divalent metal ions, the kind and concentration of cyclic nucleotide, the source and concentration of the modulator, and the nature of the enzyme. The effects of the modulator on guanosine 3',5'-monophosphate-dependent and adenosine 3',5'-monophosphate-dependent protein kinase holoenzymes were reproduced by using isolated catalytic subunits prepared from the respective holoenzymes.
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Donnelly et al. (1973) studied this question.
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