title: Cooperative modulation of protein kinase CK2 by separate domains of its regulatory beta-subunit.
abstract: Protein kinase CK2 ("casein kinase 2") holoenzyme is composed of two catalytic (alpha and/or alpha') and two regulatory beta-subunits. A truncated form of the beta-subunit lacking its C-terminal region (betaDelta171-215) has lost the ability to stably associate with the catalytic subunits and to display a number of properties which are mediated by structural elements still present in its sequence, notably down-regulation of catalytic activity, autophosphorylation, and responsiveness to polycationic effectors. All these functions are restored by simultaneous addition of a synthetic peptide reproducing the deleted fragment, beta170-215, which is able to associate with the catalytic subunits and to stimulate catalytic activity. This peptide includes a segment displaying significant sequence similarity with a region of cyclin A which interacts with the PSTAIRE motif of CDK2 eliciting its catalytic activity. A peptide reproducing this sequence (beta181-203), but not its derivative in which three nonpolar side chains have been replaced by polar ones, interacts with the alpha-subunit and stimulates its catalytic activity; it also partially restores the ability of truncated betaDelta171-215 to autophosphorylate. These data disclose the essential role of a structural module located between residues 181 and 203 in conferring regulatory properties to the beta-subunit of CK2.
authors.affiliation: Dipartimento di Chimica Biologica and Centro di Studio delle Biomembrane del CNR, Università di Padova, Padova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sarno
authors.forename: O
authors.initials: O
authors.lastname: Marin
authors.forename: M
authors.initials: M
authors.lastname: Boschetti
authors.forename: M A
authors.initials: MA
authors.lastname: Pagano
authors.forename: F
authors.initials: F
authors.lastname: Meggio
authors.forename: L A
authors.initials: LA
authors.lastname: Pinna
mesh_terms: D000595:Amino Acid Sequence; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D047390:Casein Kinase II; D019925:Cyclin A / Q000737:chemistry; D019281:Dimerization; D015536:Down-Regulation / Q000235:genetics; D020035:Holoenzymes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011107:Polylysine / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002147:Calmodulin; D019925:Cyclin A; D020035:Holoenzymes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D011107:Polylysine; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases