The monomeric alpha beta form of the insulin receptor exhibits much higher insulin-dependent tyrosine-specific protein kinase activity than the intact alpha 2 beta 2 form of the receptor.

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Abstract
The relationship between the structure of the insulin receptor and its kinase activity was studied on the purified receptor treated with different concentrations of dithiothreitol. An enhanced autophosphorylation of the .beta. subunit (Mr, 90,000) was observed on NaDodSO4/PAGE under reducing conditions when the receptor was treated with 0.1-0.75 mM dithiothreitol in the presence of 1 .mu.M insulin. Since we have previously observed (unpublished data) that incubation of the purified receptor with 1 mM dithiothreitol completely reduced an intact form of the receptor, .alpha.2.beta.2, to free .alpha. subunit (Mr, 125,000) and .beta. subunit, the population of disulfide-linked complexes of the receptor after the dithiothreitol treatment was analyzed by NaDodSO4/PAGE under nonreducing conditions. The same receptor preparations were assayed for tyrosine kinase activity by using an exogenous substrate. Treatment of the receptor with dithiothreitol significantly enhanced both basal and insulin-dependent kinase activity. The kinase activity was enhanced 12- to 37-fold at concentrations of 0.5-0.75 mM dithiothreitol in the presence of 1 .mu.m insulin. The amount of .alpha.2.beta.2, .alpha..beta., and .beta. forms in each dithiothreitol-treated receptor preparations was quantified and compared with its kinase activity. These studies clearly indicate a correlation between the appearance of an .alpha..beta. form and an increase in kinase activity. Therefore, we conclude that the .alpha..beta. form of the insulin receptor exhibits much higher kinase activity than the intact receptor in the .alpha.2.beta.2 form.