Dissecting subdomains involved in multiple functions of the CK2 beta subunit

We have characterized several subdomains of the beta subunit of protein kin ase CK2. The N-terminal half of the protein exhibits a pseudo-substrate seg ment in tandem with a polyamine binding domain responsible for the activati on of the kinase by these polybasic compounds. Study of the chemical featur es of this polyamine binding site showed that polyamine analogs exhibiting the highest affinity for CK2 are the best CK2 activators. Mutational analys is disclosed that glutamic residues lying in the polyacidic region of the C K2 beta subunit are involved in the interaction with polyamine molecules an d allowed the delineation of an autonomous binding domain. Furthermore, thi s regulatory domain was shown to mediate the association of CK2 with plasma membrane. The C-terminal domain of the CK2 beta subunit plays a role in the oligomeri zation of the kinase since it was observed that a truncated form of this su bunit lacking its 33-last amino acids was incompetent for the assembly of p olymeric forms of CK2. Altogether, our results support the notion that the beta subunit of CK2 is a modular protein made by the association of interde pendent domains that are involved in its multiple functions.