Reevaluation of the evidence that an antibody to the insulin receptor is insulinmimetic without activating the protein tyrosine kinase activity of the receptor.
The immunoglobulin fraction of a polyclonal anti-insulin receptor antibody (B-10) derived from a patient with severe insulin resistance and acanthosis nigricans was tested for its ability to activate the protein kinase activity of the insulin receptor and to mimic insulin action in Chinese hamster ovary cells expressing either wild type or kinase-deficient human insulin receptors. This antiserum had previously been reported to be insulinmimetic without activating the insulin receptor protein tyrosine kinase. Antibody B-10 bound to both wild type and mutant human insulin receptors, but it induced receptor down-regulation and stimulated hexose transport and thymidine incorporation into DNA only in cells expressing the wild type receptor. Furthermore, this antibody activated the kinase activity of the wild type insulin receptor in intact cells and in vitro. It is likely, therefore, that the biological activities of antibody B-10, like those of insulin, depend upon the protein tyrosine kinase activity of the insulin receptor.
Gherzi
R
R
Memorial Sloan-Kettering Cancer Center, New York, New York.
Russell
D S
DS
Taylor
S I
SI
Rosen
O M
OM
D000052:Acanthosis Nigricans / Q000150:complications; D000906:Antibodies; D004247:DNA / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism
D000906:Antibodies; D009004:Monosaccharide Transport Proteins; D004247:DNA; D003847:Deoxyglucose; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D013936:Thymidine