MODULATION OF THE PROTEIN-KINASE CK2 ACTIVITY BY A SYNTHETIC PEPTIDE CORRESPONDING TO THE N-TERMINUS OF ITS BETA-REGULATORY SUBUNIT

Using a synthetic peptide corresponding to the sixteen amino-acid N-te rminus of the beta subunit, the structure-activity relationship study of casein kinase 2 (CK2) was performed with regard to its previously r eported property to polymerize and oligomerize in vitro. Velocity sedi mentation experiments show that the peptide beta 1-16 prevents the thi ck filament formation and stabilizes the ring-like structure of the ki nase. Furthermore, the peptide beta 1-16 stimulates the kinase activit y by 3-fold toward exogenous substrates as well as the intrinsic autop hosphorylation of the kinase. Such observations are in agreement with the proposed model of an activated state of CK2 when the ring-like str ucture is adopted. Comparison of the effects of spermine and peptide b eta 1-16 on CK2 structure and activity suggests that these two activat ing molecules may function in a different way. Our study suggests that the N-terminal region of the beta subunit of CK2 could regulate the k inase activity by controling the quaternary structure of the enzyme. ( C) 1997 Academic Press.