Cooperative modulation of protein kinase CK2 by separate domains of its regulatory beta-subunit

Protein kinase CK2 ("casein kinase 2") holoenzyme is composed of two cataly tic (alpha and/or alpha') and two regulatory beta-subunits. A truncated for m of the beta-subunit lacking its C-terminal region (beta Delta 171-215) ha s lost the ability to stably associate with the catalytic subunits and to d isplay a number of properties which are mediated by structural elements sti ll present in its sequence, notably down-regulation of catalytic activity, autophosphorylation, and responsiveness to polycationic effectors. All thes e functions are restored by simultaneous addition of a synthetic peptide re producing the deleted fragment, beta 170-215, which is able to associate wi th the catalytic subunits and to stimulate catalytic activity. This peptide includes a segment displaying significant sequence similarity with a regio n of cyclin A which interacts with the PSTAIRE motif of CDK2 eliciting its catalytic activity. A peptide reproducing this sequence (beta 181-203), but not its derivative in which three nonpolar side chains have been replaced by polar ones, interacts with the alpha-subunit and stimulates its catalyti c activity; it also partially restores the ability of truncated beta Delta 171-215 to autophosphorylate. These data disclose the essential role of a s tructural module located between residues 181 and 203 in conferring regulat ory properties to the beta-subunit of CK2.