Indication of different lactogen and somatogen binding sites in the human growth hormone molecule as probed with monoclonal antibodies.
The relationship between the structure of human growth hormone (hGH) and the hormone-receptor interaction has been investigated using as probes monoclonal antibodies (Mabs) to hGH of defined epitope specificity profile. Seven high affinity Mabs were studied for their ability (i) to inhibit the binding of 125I-hGH to Nb2-SP rat lymphoma cells and to IM-9 human lymphocytes possessing lactogen and somatogen type receptors, respectively; and (ii) to interfere with the hormone (hGH or Met8Leu hGH)-induced proliferation in Nb2-11C lymphoma cells. The ability of these Mabs to inhibit the 125I-hGH binding and the hormone-induced proliferation in Nb2-11C cells was negatively correlated with the ability of these Mabs to cross-react with met14 hGH. Furthermore, Mabs Nos. 3 and 7, which cross-reacted minimally (0.2-0.4%) with Met8Leu hGH, were unable to interfere with the mitogenic activity of Met8Leu hGH in Nb2-11C cells. These results indicate that the first 13 amino acids of the N-terminal region of hGH are necessary for its lactogen activity. The inhibition of 125I-hGH binding to IM-9 cells by these Mabs was similar to those observed in Nb2-SP cells, except for Mabs Nos. 19 and 1. These Mabs inhibited more strongly the binding of 125I-hGH to IM-9 than to Nb2 cells and recognized antigenic epitopes close to the C-terminal part of the molecule. These results suggest that the somatogen receptor binding site of hGH may be located on two sites, one at the N-terminal and the other one close to the C-terminal, while the lactogen receptor is mainly confined to the N-terminal part.
Strasburger
C J
CJ
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Binder
L
L
Elberg
G
G
Cohen-Chapnik
N
N
Kohen
F
F
Gertler
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D013006:Growth Hormone / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008223:Lymphoma; D051381:Rats; D011986:Receptors, Somatotropin / Q000145:classification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011986:Receptors, Somatotropin; D013006:Growth Hormone