Insulin, the major hormonal regulator of glucose transport in humans, has served as a
prototypic molecule for understanding cell signaling pathways since its discovery in 1922. It
was among the first proteins for which primary amino acid sequence and threedimensional
structure were determined. The insulin receptor was likewise among the first peptide
receptors to be identified by ligand binding, and its subunit structure was deduced in the
earliest days of modern receptor biology (1). The structure of its tyrosine kinase domain was …