Nerve growth factor and insulin: evidence of similarities in structure, function, and mechanism of action

The hypothesis that nerve growth factor (NGF) and insulin have evolved from a common ancestral precursor was originally formulated based on similarities at the widely separated levels of primary structure and biological function. The usefulness of the hypothesis has been in narrowing the conceptual gap between these two. Experiments extending the structural comparison of NGF and insulin to include secondary and tertiary structure, have at the same time revealed several structure function correlations of NGF. The three dimensional structure of NGF possesses the unique conformation required for specific interaction with a receptor on the surface membrane of responsive neurons which has properties similar to the insulin receptor. At this point studies on the intracellular post receptor mechanism of either insulin or NGF should greatly contribute to an understanding of the mechanism of the other. A further consequence of the NGF insulin relationship is that it provides for comparative study two evolutionarily related hormone receptor pairs, a system which should be very useful in studying the evolutionary development of receptor mediated intercellular regulatory systems. Finally, these studies indicate that such a hormonelike regulatory system operates on a specific part of the nervous system during its embryonic development.