INSULIN-RECEPTOR AUTOPHOSPHORYLATION AND EXOGENOUS SUBSTRATE PHOSPHORYLATION - ROLE OF RECEPTOR C-TERMINUS AND EFFECTS OF MILD REDUCTION

A mutant insulin receptor lacking the final 69 amino acids of the beta-subunit (Delta 69) was used to examine the role of the receptor C-terminal domain in kinase activation. With increasing deletion of the C-terminus from 43 to 69 amino acids we show that exogenous peptide kinase activity is lost before autokinase activity. Despite this, phosphorylation of an in vivo insulin receptor substrate, IRS-1, and insulin bioeffects are similar to wild-type. In addition, with the exception of insulin-stimulated peptide phosphorylation, the reductant glutathione modified kinase activity in a similar manner for both wild-type and mutant Delta 69 receptors. These results suggest that conformational changes proposed to occur within the receptor C-terminus upon insulin binding may not be necessary for kinase activation under a variety of conditions. (C) 1994 Academic Press, Inc.