title: Receptor cross-linking restores an insulin metabolic effect altered by mutation on tyrosine 1162 and tyrosine 1163.
abstract: The pivotal role that the tyrosine residues in positions 1162 and 1163 play in the control of the insulin action has been clearly established by substitution of these tyrosine residues for phenylalanine [Ellis, L. (1986) Cell 45, 721-732]. We have recently found that this type of mutation, which abolishes the effects of insulin on glucose metabolism, was without any effect on the mitogenic effect of the hormone [Debant, A. (1988) Proc. Natl. Acad. Sci. U.S.A. (in press)]. Here, we provide evidence that a polyclonal antibody, raised against the human insulin receptor, can restore the receptor-mediated stimulation of glycogen synthesis that was abolished by the mutation. Stimulation of the biological effect by the anti-receptor antibody did not necessitate, whatsoever, the activation of the tyrosine kinase activity and/or receptor autophosphorylation. Furthermore, the antibody-induced reversal of the mutation was not observed when we used Fab fragments alone, but addition of anti-(Fab')2 IgG in a second step resulted in a similar effect as that observed with intact IgG. We propose that Tyr 1162 and Tyr 1163 exert their control on the metabolic effects of insulin through the modulation of receptor aggregation.
authors.affiliation: Unité INSERM 210, Faculté de Médecine, Nice, France.
authors.forename: A
authors.initials: A
authors.lastname: Debant
authors.forename: G
authors.initials: G
authors.lastname: Ponzio
authors.forename: E
authors.initials: E
authors.lastname: Clauser
authors.forename: J O
authors.initials: JO
authors.lastname: Contreres
authors.forename: B
authors.initials: B
authors.lastname: Rossi
mesh_terms: D000818:Animals; D000906:Antibodies; D002460:Cell Line; D006003:Glycogen / Q000096:biosynthesis; D007074:Immunoglobulin G; D007328:Insulin / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D007328:Insulin; D014443:Tyrosine; D006003:Glycogen; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin