Flexing their muscles: the discovery of myosin phosphorylation

The classic Biochemical Journal paper by Perrie, Smillie and Perry1, A phosphorylated light-chain component of myosin from skeletal muscle (1973), is a beautiful example of the long-term impact of rigorous biochemical detective work. In essence, the authors had previously observed that one of the three light-chain subunits of skeletal muscle myosin II detected by SDS/PAGE could be separated into two protein bands by charge gel electrophoresis in the presence of urea2. The key advance reported in this paper1 was the characterization of the difference between the two proteins: the species migrating more rapidly towards the anode was shown to be a phosphorylated form of the slower-migrating polypeptide. This discovery turned out to have profound biological implications.