Insulin receptor: tyrosine kinase activity and insulin action.

The first step in insulin action consists in binding of the hormone to specific cell surface receptors. This receptor displays two functional domains: an extracellular alpha-subunit containing the majority or the totality of the hormone binding site and an intracellular beta-subunit possessing insulin-stimulated tyrosine kinase activity. A general consensus has been reached in favour of the idea that this receptor enzymic function is essential for generation of the metabolic and growth-promoting effects of insulin. Concerning the mechanism of transmembrane signalling, we like to think that interaction of insulin with the receptor alpha-subunit triggers a conformational change, which is propagated to the beta-subunit and activates it. The active receptor kinase leads then to the phosphorylation of cellular protein substrates, which are likely to belong to two broad categories, those generating metabolic effects of insulin and those resulting in growth-promoting effects. The phosphorylated and active substrates then generate the final effects of insulin.