STRUCTURAL REQUIREMENTS OF A RAT LIVER PROTEINKINASE DISPLAYING A SPECIFICITY SIMILAR TO THAT OF THE MAMMARY GLAND CASEINKINASE(S)

Abstract

Three Threonyl and at least six Seryl residues phosphorylated in five different model protein substrates by Caseinkinase TS (CK-TS), a cAMP-independent proteinkinase whose function in the rat liver cytosol is still obscure, have been identified. All of them are located at the N terminal side of two or more acidic residues, within segments having an high probability of occurrence as β-turns. Most of the Phosphoseryl residues of native caseins display the same features. Moreover all the four typical (Ser-P)3 clusters of αs1, αs2, and β-caseins can be phosphorylated also by CK-TS after partial dephosphorylation. CNBr and Trypsin digestion of αs2-casein promotesa remarkable fall of the phosphorylation rate of residues still included in relatively large peptides, suggesting that the CK-TS activity might be optimized by a definite size or shape of the protein substrate. The striking specificity of the “so-called” rat liver Casein kinase TS for the same sites phosphorylated in vivo by the “true” mammary gland Caseinkinase suggests as a working hypothesis that these two enzymes, though playing different roles, might be related to each other.