Discrete region of the insulin receptor carboxyl terminus plays key role in insulin action

In the present study, we attempted to determine the importance of a 23-amin o-acid sequence within the carboxyl terminus of the human insulin receptor (IR) molecule in modulating insulin action in Chinese hamster ovary cells. Stable expression of a minigene encoding the receptor fragment led to an in crease in insulin-induced IR autophosphorylation that was 2.4-fold higher w hen compared to that of IR-expressing cells transfected with empty vector. Insulin-stimulated downstream signaling was also significantly elevated in cells expressing the minigene. It was found that expression of the minigene had no effect toward insulin-like growth factor I receptor kinase activity and function. These results indicate that the IR carboxyl terminus contain s a motif that acts as a physiologic modulator of insulin signaling. Publis hed 2000 Wiley-Liss, Inc.(dagger).