Characterization of an Antagonist Monoclonal Antibody, GHBP116,Specific for Human Growth Hormone Receptors

概要

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To obtain an antagonist antibody against human growth hormore receptors (hGHRs), we prepared monoclonal antibodies against the recombinant hGHR extracellular domain. One of the clones, GHBP116,exhibited binding activity to intact human IM-9 cells and effectively immunoprecipitated the receptors in cell lysate. GHBP116 competitively inhibited ^<125>I-human growth hormore (hGH) binding to the cells. The antagonist activity of GHBP116 was assessed in terms of ligand-induced receptor internalization, degradation, and phosphorylation of signal transducer and activator of transcription (STAT) 5. The antibody alone did not cause internalization or degradation of hGHRs, but a 1 : 25000 dilution of ascitic fluid almost completely inhibited ligand (1 nM hGH)-induced internalization and degradation of surface hGHRs. Moreover, GHBP116 alone did not stimulate the phosphorylation of STAT5,used as an indicator of Janus kinase (JAK)-STAT signaling, but almost completely inhibited hGH-induced phosphorylation of STAT5. These results suggest that GHBP116 acts as a specific antagonist of hGH.
社団法人日本薬学会の論文
1999-07-15