Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate postreceptor effects of insulin.

摘要: Transfected Chinese hamster ovary cell lines were developed that expressed equivalent numbers of either normal human receptor or had alanine substituted for Lys-1018 in the ATP-binding domain beta subunit. The mutated was processed into subunits and bound insulin but lacked protein tyrosine kinase activity. Five effects assayed: deoxyglucose uptake, S6 activity, endogenous protein-tyrosine phosphorylation, glycogen synthesis, thymidine uptake. In each case, cells bearing receptors 10-100-fold more sensitive to than parental cells. Cells with mutant behaved like respect activation, substrate their uptake significantly depressed relatively insensitive insulin. analyses led following conclusions: substitution lysine at amino acid 1018 inactivates activity receptor; a kinase-negative can be properly bind insulin; insulin-dependent incorporation DNA are mediated by not kinase-deficient receptor.