"Genuine" Casein Kinase (Fam20C): The Mother of the Phosphosecretome

Although several members of the kinome are able to phosphorylate casein in vitro, notably casein kinase 2 (CK2) and the members of the casein kinase 1 (CK1) subfamily, none of these enzymes are the bona fide casein kinase (Golgi casein kinase (G-CK)) whose activity was detected and partially purified from the Golgi apparatus of lactating mammary gland and milk. Although casein was the first protein shown to contain phosphate esterified to phosphoseryl residues, the sequences surrounding the phosphoseryl residues of casein fractions started being elucidated almost one century later in 1971. In the meantime, the amino acid sequences surrounding residues in fibrinogen had been elucidated, revealing the same pS-x-E motif, later also found in pepsin, corticotropin, ovalbumin, and in all casein fractions. Peptide (ß28-40) exhibits an unmatched selectivity among the huge repertoire of protein kinase peptide substrates being unaffected only by all the false "casein kinases," including CK1 and CK2.