Insulin/IGF-I receptor hybrids: A mechanism for increasing receptor diversity

Abstract

Insulin and IGF‐l receptors are homologous disulfide linked α₂β₂ tetramers. These tetramers are formed biosynthetically when proreceptors containing α and β subunits in a single uninterrupted linear peptide from disulfide linked homodimers and are subsequently proteolytically cleaved at the α‐β junctions. Cells expressing both receptors also express hybrid receptors that contain one insulin receptor α and β subunit, and one IGF‐l receptor α and β subunit. These presumably from by the association of mixed proreceptors. Hybrid receptors greatly expand the possible repertoire of cellular responses to hormonal stimulation. Although not yet examined in detail, both the hormone binding and the signaling properties of the hybrid receptor appear to be different from that of either insulin or IGF‐l receptor. Regulatory mechanisms that involve either insulin or IGF‐l receptor, at the level of expression or subsequently, could alter the expression or function of the hybrid receptor or the other receptor. Similarly, pathology in one receptor could affect both the hybrid and other receptor, or perhaps be partially compensated for by a hybrid receptor. The magnitude of these effects could vary greatly in different tissues depending upon the relative level of expression of the different receptor forms. These postulated responses might explain some of the complex heterogeneity and linkage of these receptors that have been observed previously.