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Autoantibodies to the Insulin Receptor (B-10) Can Stimulate Tyrosine Phosphorylation of the β-Subunit of the Insulin Receptor and a 185,000 Molecular Weight Protein in Rat Hepatoma Cells^*

Third Department of the Internal Medicine, Faculty of Medicine, University of Tokyo (S.T.-H., K.M., F.T., M.K.)₉ 7-3-1 Hongo Bunkyo-Ku, Tokyo, Japan 113
The Diabetes Center, Tokyo Women’s Medical College (S.T.-H., Y.H) Kawada-cho, Shinjuku-Ku, Tokyo, Japan 162
The Institute of Diabetes Care and Research, Asahi Life Foundation (K.T., O.K., Y.T.-H., Y.A., M.K.) 1-6-1 Marunouchi, Chiyoda-Ku, Tokyo, Japan 100

Address requests for reprints to: Masato Kasuga, M.D., Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan 113.

The immunoglobulin G (IgG) fraction obtained from the serum of a patient (B-10) with type B insulin resistance and acanthosis nigricans stimulated both glucose oxidation in rat adipocytes and autophosphorylation of tyrosine residues in the β-subunit of insulin receptors in H-35 hepatoma cells. Partially purified insulin receptor from H-35 cells, when incubated with B-10 IgG, had increased tyrosine kinase activity for a synthetic peptide sequentially similar to the site of tyrosine phosphorylation in pp6O^v-8rc (the gene product responsible for cellular transformation by the Rous sarcoma virus). In H-35 cells, both B-10 IgG and insulin stimulated tyrosine phosphorylation in an endogenous 185,000 mol wt protein. This phosphoprotein may be similar to the cellular substrate for insulin in hepatoma and other cultured cell lines demonstrated by others. These results suggest that antiinsulin receptor antibodies (B-10) may initiate their insulin-like effects via tyrosine phosphorylation of the insulin receptor, activation of its tyrosine kinase activity, and phosphorylation of a cellular protein substrate of 185,000 mol wt.

^* This work was supported in part by a Grant-in-Aid for Developmental Scientific Research from the Ministry of Education, Science, and Culture of Japan, a grant from the Kato Memorial Trust for Nambyo Research, a Grant from Hoansha, and a Grant from the Uehara Memorial Foundation.

Received June 1, 1988.