Polyglutamyl peptides: a new class of inhibitors of type-2 casein kinases.
Casein kinase-TS (Ck-TS), a type-2 casein kinase purified from rat liver cytosol which phosphorylates seryl and threonyl residues N-terminal to acidic clusters, is specifically inhibited by polyglutamyl peptides which are ineffective both on type-1 casein kinase and on cAMP-dependent protein kinase. The inhibition is competitive toward the protein substrate and non-competitive toward ATP. Among the polyglutamates tested (Glu)70 is the most effective (Ki 0.11 microM). (Glu)10 and (Glu)5 are also inhibitors, though less powerful than (Glu)70, while (Glu)3, (Glu)2 and free glutamic acid up to 5 mM are ineffective. These results disclose the possibility that naturally occurring polypeptides containing long stretches of acidic residues may act as physiological inhibitors of type-2 casein kinases.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D047388:Casein Kinases; D003600:Cytosol / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000302:isolation & purification; D051381:Rats; D013329:Structure-Activity Relationship
D010455:Peptides; D047428:Protein Kinase Inhibitors; D011099:Polyglutamic Acid; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D047388:Casein Kinases