Purification of Insulin and Insulin-Like Growth Factor (IGF)-I Receptor

Abstract

Peptide hormone/growth factor receptors are membrane glycoproteins. The receptor specifically binds its ligand, which approaches the cell from the outside, transduces the signal to the inside, and, consequently initiates biological programs specific to the receptor-ligand complex. In the case of insulin and IGF-I, the ligands not only share amino acid sequence homology (Rinderknecht and Humbel, 1978; Blundell et ai., 1978), but also the receptors are structurally and functionally similar (Jacobs et ai., 1983; Rechler and Nissley, 1985; Fujita-Yamaguchi et al., 1986). Recent progress made in purification and subsequent cloning of both receptors revealed ~60% identity in their overall amino acid sequence (Ullrich et al., 1985; Ebina et ai., 1985; Ullrich et ai., 1986). The receptors for insulin and IGF-I consist of α and β subunits, linked in a β-α-α-β form by disulfide bonds. The α subunit of M_r = ~125,000 is extracellular and responsible for ligand binding, whereas the β subunit of M_r = ~90,000 is a transmembrane protein carrying a tyrosine-specific protein kinase in its cytoplasmic domain. When the specific ligand binds to the extracellular domain, the β subunit kinase is activated, and consequently, phosphorylates itself (autophosphorylation) as well as intracellular components (Rees-Jones and Taylor, 1985; White et al., 1985; Bernier et al., 1987).