Calmodulin stimulates polyamine-responsive protein kinase in the absence of Ca2+.
A cyclic nucleotide-independent, polyamine-responsive protein kinase from the cytosol of Morris hepatoma 3924A, which phosphorylated heat-stable endogenous substrates and casein in the presence of polyamines (Criss, W.E., Yamamoto, M., Takai, Y., Nishizuka, Y. and Morris, H.P. (1978) Cancer Res. 38, 3540-3545) was observed to be stimulated by an endogenous protein activator. This protein activator was identified to be calmodulin. the polyamine-responsive protein kinase was also stimulated by purified calmodulin, but only in the presence of polyamines such as polylysine. This action of calmodulin did not require Ca2+ for activation of the enzyme; and activation occurred in the presence of EGTA. DNA and RNA inhibited the polyamine-responsive protein kinase, either in the presence or absence of Ca2+. Purified calmodulin, in the presence of cyclic AMP or cyclic GMP, did not activate the protein kinase. Therefore, polyamines such as polylysine are an absolute requirement for this expression of calmodulin action. The increased enzyme activity by calmodulin was accompanied with an increased Vmax and with no changes in the Km (ATP). High levels of cation, up to 100 mM Mg2+, did not effect the action of calmodulin. These results indicate that tumor cytosolic polyamine-responsive protein kinase is regulated by calmodulin, the latter being increased in the tumor tissue.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D002417:Cattle; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology; D008274:Magnesium / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D011073:Polyamines; D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP; D008274:Magnesium; D002118:Calcium