Cooperative Modulation of Protein Kinase CK2 by Separate Domains of Its Regulatory β-Subunit

• Published in: Biochemistry (Easton) 2000-10, Vol.39 (40), p.12324-12329
• Main Authors: Sarno, Stefania, Marin, Oriano, Boschetti, Marco, Pagano, Mario A, Meggio, Flavio, Pinna, Lorenzo A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Calmodulin - antagonists & inhibitors; Calmodulin - metabolism; Casein Kinase II; Cyclin A - chemistry; Dimerization; Down-Regulation - genetics; Holoenzymes - chemistry; Holoenzymes - metabolism; Humans; Molecular Sequence Data; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - metabolism; Phosphorylation; Polylysine - chemistry; Protein Structure, Tertiary - genetics; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Recombinant Proteins - chemical synthesis; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Up-Regulation - genetics
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi0011431

Protein kinase CK2 (“casein kinase 2”) holoenzyme is composed of two catalytic (α and/or α‘) and two regulatory β-subunits. A truncated form of the β-subunit lacking its C-terminal region (βΔ171−215) 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, β170−215, 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 A peptide reproducing this sequence (β181−203), but not its derivative in which three nonpolar side chains have been replaced by polar ones, interacts with the α-subunit and stimulates its catalytic activity; it also partially restores the ability of truncated βΔ171−215 to autophosphorylate. These data disclose the essential role of a structural module located between residues 181 and 203 in conferring regulatory properties to the β-subunit of CK2.