Banting lecture 1989. Structure and function of insulin receptors.

The actions of insulin are mediated by an integral plasma membrane protein, the insulin receptor. The processed receptor is a tetramer composed of two alpha-subunits that bind insulin and two beta-subunits that traverse the plasma membrane and are, in their cytosolic domains, protein tyrosine kinases. The insulin proreceptor cDNA has been cloned and its complete amino acid sequence deduced. The availability of cDNA permitted an analysis of both the role of protein tyrosine kinase activity in insulin action and the autophosphorylation sites that regulate kinase activity. The human cDNA probe has also been used to identify a putative Drosophila insulin receptor. This work is reviewed, and approaches that may be used to identify physiological substrates for the receptor kinase are suggested.