title: Casein kinase 2 down-regulation and activation by polybasic peptides are mediated by acidic residues in the 55-64 region of the beta-subunit. A study with calmodulin as phosphorylatable substrate.
abstract: The noncatalytic beta-subunit is responsible for the latency of casein kinase 2 (CK2) activity toward calmodulin. Twenty-one mutants of the beta-subunit bearing either deletions or Ala substitutions for charged residues in the 5-6, 55-70, and 171-178 sequences have been assayed for their ability to substitute for wild-type beta-subunit as a suppressor of activity toward calmodulin. The only mutations that reduced the ability of the beta-subunit to suppress calmodulin phosphorylation activity, though being compatible with normal reconstitution of CK2 holoenzyme, were those affecting Asp55, Glu57 and the whole triplet Glu59-Asp-Glu61. The activity of CK2 holoenzyme, either native or reconstituted, toward calmodulin can be elicited by a variety of polybasic effectors, including polylysine, polyarginine, salmine, and histones H4, H3, and, to a lesser extent, H2a and H2b. Histone H1 and polyamines are conversely ineffective. The latent "calmodulin kinase" activity of CK2 can also be specifically unmasked by a peptide (alpha[66-86]) reproducing a basic insert of the catalytic subunit. This effect is reversed by equimolar addition of a peptide (beta[55-71]) including the 55-64 acidic stretch of the beta-subunit. Comparable polylysine stimulation was observed with the holoenzymes reconstituted with either beta wt or the beta mutants capable of assembling with the alpha-subunit, with the notable exception of those bearing Ala substitutions for acidic residues at positions 55, 57, and 59-61. These were nearly insensitive to 42 nM polylysine, which conversely promotes a more than 10-fold increase of calmodulin phosphorylation with wild-type beta.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Dipartimento di Chimica Biologica, Università di Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Meggio
authors.forename: B
authors.initials: B
authors.lastname: Boldyreff
authors.forename: O G
authors.initials: OG
authors.lastname: Issinger
authors.forename: L A
authors.initials: LA
authors.lastname: Pińna
mesh_terms: D000595:Amino Acid Sequence; D002147:Calmodulin / Q000378:metabolism*; D047388:Casein Kinases; D015536:Down-Regulation; D004789:Enzyme Activation; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D047388:Casein Kinases; D010446:Peptide Fragments; D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers; D011494:Protein Kinases