| Abstract: | Based on the finding that stimulation of the IGF-II, receptor (IGF-IIR) is capable of activating Gi2 and calcium channels in BALB/c 3T3 fibroblasts, it was found that purified IGF-IIR can couple directly to purified Gi2 in phospholipid vesicles. IGF-IIR–Gi2 coupling can be characterized as follows. IGF-IIR directly couples to Gi2 in response to IGF-II in a stoichiometrical manner, suggesting that IGF-IIR works as a transmembrane signaling molecule and that the seven-transmembrane structure is not essential for receptor-G protein coupling. The mode of IGF-IIR–Gi2 interaction is similar to that of conventional receptor–G protein coupling, suggesting that a common G protein recognition mechanism is shared by IGF-IIR and conventional G-coupled receptors. The action of IGF-IIR is specific on Gi2 among various G proteins. Finally, the activity of IGF-IIR on Gi2 is similarly potent across the species of the proteins. These characteristics led to the discovery of a 14-amino-acid region in IGF-IIR that can directly interact with and activate Gi2, and is located at residues 2410–2423 of the human receptor. Subsequent work has indicated that this region is responsible for Gi-coupling function of intact IGF-IIR. The most important extensions of this discovery are the following: (1) The structure–function relationship for the Gi-activating function of this 14-amino-acid sequence, (2) the prediction of G protein-coupled functions of receptors based on the results obtained from 1), and (3) clarification of the detailed mechanism whereby ligand–receptor complex recognizes G proteins. This paper reviews what we have learned from IGF-IIR in terms of receptor–G protein interfaces and discusses future prospects. © 1993 Wiley-Liss, Inc. |
