Positive cooperative effects between receptors induced by an anti-human growth hormone allosteric monoclonal antibody.
Monoclonal antibodies (MAb) anti-human growth hormone (hGH) termed MAb AE5, AC8 and F11 recognize a cluster of epitopes left exposed after hormone binding to receptors. Since these MAb were able to produce either positive (MAb AE5) or negative (MAb AC8 and F11) allosteric effects on hGH binding, the purpose of this work was to further characterize MAb behavior. Results indicated a straight correlation between MAb allosteric effects and affinity constant values for binding of different hGH:MAb complexes to lactogenic receptors from rat liver. Affinity of hGH:MAb AE5 as well as hGH:Fab AE5 complexes enhanced proportionally to the fraction of occupied receptors and Hill coefficients higher than 1 were obtained, suggesting the induction of positive cooperative effects between membrane-bound receptors. On the other hand, hGH:MAb AC8 and hGH:MAb F11 complexes binding affinity to lactogenic sites could not be related to receptor occupancy degree. It is proposed that binding of hGH:MAb AE5 complexes to receptors would elicit a conformational change on adjacent receptor molecules leading to an increase of their affinity to bind subsequent hGH:MAb AE5 complexes.
Aguilar
R C
RC
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
Blank
V C
VC
Retegui
L A
LA
Roguin
L P
LP
D000494:Allosteric Regulation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D005260:Female; D013006:Growth Hormone / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011986:Receptors, Somatotropin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D011986:Receptors, Somatotropin; D013006:Growth Hormone