Phosphorylation of src-phosphopeptides by casein kinases-1 and -2: favourable effect of phosphotyrosine

• Published in: Biochemical and biophysical research communications Vol. 170; no. 2; p. 635
• Main Authors: Perich, J W, Meggio, F, Kitas, E A, Valerio, R M, Johns, R B, Pinna, L A
• Format: Journal Article
• Language: English
• Published: United States 31-07-1990
• Subjects: Amino Acid Sequence; Brain - enzymology; Casein Kinases; Hydrogen-Ion Concentration; Kinetics; Molecular Sequence Data; Phosphopeptides - metabolism; Phosphorylation; Phosphotyrosine; Protein Kinase C - pharmacology; Protein Kinases - pharmacology; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Substrate Specificity - drug effects; Tyrosine - analogs & derivatives; Tyrosine - pharmacology
• ISSN: 0006-291X
• DOI: 10.1016/0006-291X(90)92139-Q

The synthetic phosphotyrosyl tridecapeptide H-Arg-Leu-Ile-Glu-Asp-Asn-Glu-Tyr(P)-Thr-Ala-Arg-Gln-Gly-OH, reproducing a major phosphoacceptor site of protein tyrosine kinases of the src-family, can be phosphorylated at Thr-9 by both casein kinases -1 and -2. Its shorter derivative H-Asn-Glu-Tyr(P)-Thr-Ala-OH is not affected by casein kinase-1 while representing a substrate as good as the tridecapeptide for casein kinase-2. The unphosphorylated analogue H-Asn-Glu-Tyr-Thr-Ala-OH, however, is a much poorer substrate, and no significant phosphorylation could be observed of its O-methyl ether derivative H-Asn-Glu-Tyr(Me)-Thr-Ala-OMe. These data on one side corroborate the concept that casein kinase-1 recognizes residues located on the C-terminal edge of acidic stretches, providing, on the other, the evidence that phosphotyrosyl side chains can act as specificity determinants for casein kinase-2.