Glycogen Synthase from Rabbit Skeletal Muscle: Amino Acid Sequence at the Sites Phosphorylated by Glycogen Synthase Kinase‐3, and Extension of the N‐Terminal Sequence Containing the Site Phosphorylated by Phosphorylase Kinase

Glycogen synthase kinase‐3 phosphorylates three serine residues on glycogen synthase (sites 3a, 3b and 3c) which are all located in the same nine‐amino‐acid segment of the polypeptide chain. The sequence in this region is: Arg‐Tyr‐Pro‐Arg‐Pro‐Ala‐Ser(P)‐Val‐Pro‐Pro‐Ser(P)‐Pro‐Ser‐Leu‐Ser(P)‐Arg‐. These serine residues are distinct from the sites phosphorylated preferentially by cyclic‐AMP‐dependent protein kinase (sites 1a and 1b) and phosphorylase kinase (site 2). The N‐terminal sequence of glycogen synthase containing the serine residue phosphorylated by phosphorylase kinase has been extended. The sequence in this region is: Pro‐Leu‐Ser‐Arg‐Thr‐Leu‐Ser(P)‐Val‐Ser‐Ser‐Leu‐Pro‐Gly‐Leu‐Glu‐Asp‐Trp‐Glu‐Asp‐Glu‐Phe‐Asp‐Leu‐Glu‐Asn‐Ser‐Val‐Leu‐Phe‐(Asx₂,Glx₂,Ala₂,Val₂,Lys)‐. The similarity to the N‐terminal sequence of phosphorylase is confined to the immediate vicinity of the phosphorylation site (residues 4–15). The relationship of glycogen synthase kinase‐3 to glycogen synthase kinases that have been described by other laboratories is discussed.