Alternative IGF-Related Receptors

Abstract

A substantial number of reports over more than a decade have described variant forms of receptors for insulin-like growth factors (IGFs) and insulin, which differ in structure or ligand specificity from classic type I IGF receptors and insulin receptors as characterized in most mammalian tissues or by expression of their cloned cDNAs. As an introduction to receptor subtypes, we first describe briefly the structure and function of the insulin receptor (IR), type I IGF receptor (IGFR), and insulin-receptor-related receptor (IRR), as reflected in the products of their cloned genes. We then review the properties of known splice variants of these receptors, which represent an obvious potential source of functional heterogeneity. Next, we discuss “atypical” insulin and IGF receptors that apparently bind both insulin and IGFs with high affinity, and attempt to rationalize anomalous observations and assess the structural basis and functional significance of these receptors. Finally we consider the properties of insulin/IGF hybrid receptors, which combine the structures and functions of both receptors and may account for much of the reported heterogeneity in receptor subtypes.