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.