Polyamines as negative regulators of casein kinase-2: the phosphorylation of calmodulin triggered by polylysine and by the alpha[66-86] peptide is prevented by spermine.
Calmodulin and other protein substrates of casein kinase-2 (CK2) are not phosphorylated by CK2 holoenzyme under basal conditions. The non catalytic beta-subunit of CK2 is responsible for such a down-regulation which can be overcome by the addition of polylysine [Meggio, F. et al. (1992) Eur. J. Biochem. 205, 939-945]. Here we show that the peptide CVVKILKPVKKKKIKREIKILE, reproducing the basic insert 66-86 of CK2 catalytic subunit, can mimick polylysine in triggering the latent "calmodulin kinase" activity of CK2 holoenzyme, and that spermine and, to a lesser extent, spermidine, but not putrescine, can reversibly and dose-dependently counteract such an activation. Spermine also abolishes the stimulation by polybasic peptides of basal CK2 activity. These findings disclose the possibility that spermine may act in vivo as a negative regulator of CK2 activity toward a category of substrates, like calmodulin and ornithine decarboxylase, whose phosphorylation is dependent on polybasic peptides.
Sarno
S
S
Dipartimento di Chimica Biologica, Università di Padova, Italy.
Marin
O
O
Meggio
F
F
Pinna
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D047388:Casein Kinases; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation; D011073:Polyamines / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology*; D013379:Substrate Specificity
D002147:Calmodulin; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011073:Polyamines; D047428:Protein Kinase Inhibitors; D011107:Polylysine; D013096:Spermine; D011494:Protein Kinases; D047388:Casein Kinases; D013095:Spermidine; D011700:Putrescine