title: Concanavalin A-induced receptor aggregation stimulates the tyrosine kinase activity of the insulin receptor in intact cells.
abstract: Concanavalin A (ConA) stimulated the phosphorylation of the beta-subunit of the insulin receptor and an Mr-185,000 protein on serine and tyrosine residues in intact H-35 rat hepatoma cells. This Mr-185,000 protein whose phosphorylation was stimulated by ConA was identical to pp185, a protein reported previously to be a putative endogenous substrate for the insulin receptor tyrosine kinase in rat hepatoma cells. In Chinese hamster ovary (CHO) cells transfected with cDNA of the human insulin receptor, tyrosine-phosphorylation of pp185 was strongly enhanced by ConA compared with the controls, suggesting that the induction of tyrosine-phosphorylation of pp185 was due to stimulation of the insulin receptor kinase by ConA. Moreover, monovalent ConA only slightly induced the tyrosine-phosphorylation of pp185, which was enhanced by the addition of anti-ConA IgG, suggesting that ConA stimulated the insulin receptor kinase mainly by the receptor cross-linking or aggregation in intact cells. These data suggest that the insulin-mimetic action of ConA is related to the autophosphorylation and activation of the insulin receptor tyrosine kinase, as well as the subsequent phosphorylation of pp185 in intact cells.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shiba
authors.forename: K
authors.initials: K
authors.lastname: Tobe
authors.forename: O
authors.initials: O
authors.lastname: Koshio
authors.forename: R
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Shibasaki
authors.forename: N
authors.initials: N
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Toyoshima
authors.forename: T
authors.initials: T
authors.lastname: Osawa
authors.forename: Y
authors.initials: Y
authors.lastname: Akanuma
authors.forename: F
authors.initials: F
authors.lastname: Takaku
mesh_terms: D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D010449:Peptide Mapping; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D003208:Concanavalin A; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin