Evidence that insulin plus ATP may induce a conformational change in the beta subunit of the insulin receptor without inducing receptor autophosphorylation.
作者： B A Maddux , I D Goldfine
DOI: 10.1016/S0021-9258(20)89560-X
关键词: Autophosphorylation 、 Biology 、 IRS2 、 Insulin-like growth factor 1 receptor 、 ATP synthase alpha/beta subunits 、 Biochemistry 、 Receptor 、 Insulin 、 Insulin receptor 、 Insulin receptor substrate 、 Endocrinology 、 Internal medicine
摘要: The effect of insulin and ATP on receptor beta subunit conformation was studied in vitro with radioiodinated monoclonal antibodies directed at several regions the subunit. Insulin plus inhibited their binding to receptor. greatest inhibitory seen antibody 17A3 which recognizes a domain that is near major tyrosine autophosphorylation sites residues 1158, 1162, 1163. alone one-half maximal concentration 186 +/- 7 microM. concentrations as low 100 pM potentiated ATP; nM where had its effect, lowered 16 6 At 1 mM CTP, GTP, ITP, TTP, AMP were without either presence or absence insulin; contrast, ADP insulin. Of interest adenyl-5'-yl imidodiphosphate (AMP-PNP). This nonhydrolyzable analog binding, AMP-PNP (like ATP) by Two mutants then studied. Mutant F3, 1163 changed phenylalanines, bound 17A3; manner similar normal receptors. In mutant M1030, lysine site residue 1030 methionine, 17A3, but unlike receptors F3 receptors, not ATP. Therefore, these studies raise possibility that, vivo, may induce conformational change turn signals some biological effects
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