The Insulin Receptor Kinase

Polypeptide hormone receptors were first identified using direct binding techniques in which radiolabeled ligands of high purity were incubated with tissue preparations, cells, or subcellular membrane fractions in the presence and absence of unlabeled hormone (Cuatrecasas et al., 1971; Freychet et al., 1971). In this manner the key receptor properties of specificity and high affinity were characterized (Roth, 1973; Posner et al., 1974). Using this relatively simple approach peptide hormone receptors were found in tissues not previously regarded as targets for the hormones (Gavin et al., 1972; Posner et al., 1973; Kelly et al., 1974). Thus insulin receptors were observed in brain and placenta in addition to being present in the classical targets of muscle, liver, and adipose tissue (Posner et al., 1973, 1974; Kelly et al., 1974). It was also soon shown that tissue peptide hormone receptor levels were modulated, and that the hormone itself played a role in both down-regulating (Gavin et al., 1974) and up-regulating (Posner et al., 1975) receptors, in part depending on ambient ligand concentration (Barash et al., 1988). Using receptor preparations it was possible to measure hormone levels in analogous fashion to radioimmunoassay except that a higher degree of hormonal integrity was assessed in radioreceptor assays (Posner et al., 1980).