Identification of an epitope shared by the DNA-binding domain of glucocorticoid receptor and the B chain of insulin.
A monoclonal antibody (8G11-C6) generated by an auto-anti-idiotypic route and directed to a site near the ligand-binding site of the glucocorticoid receptor also binds to native insulin and the B chain of insulin but not to the A chain of insulin. The glucocorticoid receptor and the B chain of insulin, therefore, share a cross-reacting epitope. Examination of the primary sequences of the two proteins revealed a limited number of regions of identity or close homology. Several peptides representative of those regions were synthesized. A heptapeptide sequence of the B chain of insulin with homology to a sequence in the first "zinc finger" of the DNA-binding domain of the glucocorticoid receptor was identified as the cross-reactive epitope. This heptapeptide sequence is restricted to and highly conserved among insulins of various species. Homologous sequences are found in the DNA-binding domains of most steroid receptors and related DNA-binding proteins. Consistent with this is the finding that 8G11-C6 inhibits the binding of glucocorticoid receptor to DNA-cellulose.
Cayanis
E
E
Department of Microbiology, Columbia University, New York, NY 10032.
Sarangarajan
R
R
Lombes
M
M
Nahon
E
E
Edelman
I S
IS
Erlanger
B F
BF
D000315:Adrenalectomy; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis*; D007328:Insulin / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D014221:Triamcinolone / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D000939:Epitopes; D007328:Insulin; D046911:Macromolecular Substances; D011965:Receptors, Glucocorticoid; D014221:Triamcinolone