Insulin receptor
insulin receptor complex
The native alpha 2 beta 2 tetramer is the only subunit structure of the insulin receptor in intact cells and purified receptor preparations.
The native subunit structure of the insulin receptor was reinvestigated by two-dimensional nonreducing/reducing gel electrophoresis. Human insulin receptor expressed in murine fibroblasts was found to be a single oligomer, the alpha 2 beta 2 heterotetramer. The structure was assessed using receptor metabolically labeled with [35S]methionine, and using receptor autophosphorylation at two levels of purification: the insulin affinity-purified receptor and the more commonly used wheat germ agglutinin-Sepharose-enriched fraction from whole membrane extracts. Lower molecular weight oligomers and free subunits were observed only upon heating the sample prior to electrophoresis. This artifact of sample handling was dependent upon three factors: (i) temperature, (ii) time of heating, and (iii) impurities typically present in partially purified receptor preparations. We conclude that the alpha 2 beta 2 tetramer is the only insulin receptor subunit structure native in intact cells and subsequently isolated from cell membranes.