Unique Specificity Determinants for an S6/H4 Kinase and Protein Kinase C: Phosphorylation of Synthetic Peptides Derived from the Smooth Muscle Myosin Light Chain

In 1977 the purification of a murine lymphosarcoma protein kinase which exhibited a high affinity for the protein substrate histone H4 was reported. Initial kinetic studies with intact histone H4 established that H4 kinase catalyzed phosphorylation of a single serine in the protein. Histone H4 contains only two serines, at residues 1 and 47. The NH₂-terminal serine is acetylated. Synthetic peptides corresponding to the H4 sequence have been used to show that H4 kinase requires the presence of a lysine-arginine sequence one residue NH₂-terminal from the modified serine for optimal activity. The NH₂-terminal amino acid sequence of the smooth muscle myosin light chain has been used to establish that the H4 kinase is not related to protein kinase C, although both enzymes catalyze phosphorylation of several common substrates. Synthetic peptides derived from the protein kinase C phosphorylation site in the light chain clearly establish that the specificity determinants for protein kinase C and H4 kinase differ.