Autoantibodies to the insulin receptor (B-10) can stimulate tyrosine phosphorylation of the beta-subunit of the insulin receptor and a 185,000 molecular weight protein in rat hepatoma cells.
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 beta-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 pp60v-arc (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.
Takayama-Hasumi
S
S
Third Department of the Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Tobe
K
K
Momomura
K
K
Koshio
O
O
Tashiro-Hashimoto
Y
Y
Akanuma
Y
Y
Hirata
Y
Y
Takaku
F
F
Kasuga
M
M
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D007074:Immunoglobulin G / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism*; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism*; D010447:Peptide Hydrolases; D010449:Peptide Mapping; D010750:Phosphoproteins / Q000032:analysis*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism*
D001323:Autoantibodies; D007074:Immunoglobulin G; D007328:Insulin; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D010447:Peptide Hydrolases