Banting lecture 1989. Structure and function of insulin receptors

Area of Science:

• Molecular biology
• Biochemistry
• Cell signaling

Background:

• Insulin action is mediated by the insulin receptor, a plasma membrane protein.
• The receptor is a tetramer with alpha-subunits binding insulin and beta-subunits possessing protein tyrosine kinase activity.
• Understanding the receptor's structure and function is crucial for elucidating insulin signaling pathways.

Purpose of the Study:

• To clone the insulin proreceptor cDNA and deduce its amino acid sequence.
• To analyze the role of protein tyrosine kinase activity in insulin action.
• To identify autophosphorylation sites regulating kinase activity and explore potential physiological substrates.

Main Methods:

• Complementary DNA (cDNA) cloning of the human insulin proreceptor.
• Amino acid sequence determination.
• Analysis of protein tyrosine kinase activity and autophosphorylation sites.
• Use of human cDNA probe to identify homologous sequences in Drosophila.

Main Results:

• The complete amino acid sequence of the human insulin proreceptor was deduced from its cDNA.
• The study provided insights into the role of protein tyrosine kinase activity in insulin receptor function.
• Potential autophosphorylation sites regulating kinase activity were identified.
• A putative Drosophila insulin receptor was identified using the human cDNA probe.

Conclusions:

• The cloning and sequencing of insulin receptor cDNA have enabled detailed functional analysis.
• Protein tyrosine kinase activity and its regulation are central to insulin receptor signaling.
• The identification of a Drosophila homolog suggests evolutionary conservation of insulin signaling mechanisms.