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: T Shiba, K Tobe, O Koshio, R Yamamoto, Y Shibasaki, N Matsumoto, S Toyoshima, T Osawa, Y Akanuma, F Takaku
• Journal: The Biochemical journal (Biochem J) Vol. 267 Issue 3 Pg. 787-94 (May 01 1990) ISSN: 0264-6021 [Print] England
• PMID: 2339989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Concanavalin A
• Protein-Tyrosine Kinases
• Receptor, Insulin

Topics

• Animals
• Concanavalin A (pharmacology)
• Cricetinae
• Dose-Response Relationship, Drug
• Humans
• Kinetics
• Peptide Mapping
• Phosphorylation
• Protein-Tyrosine Kinases (analysis)
• Rats
• Receptor, Insulin (drug effects, genetics, metabolism)
• Transfection