Intracellular signaling transduction pathways triggered by a well-known anti-GHR monoclonal antibody, Mab263, in vitro and in vivo

Abstract

A series of studies have reported that monoclonal antibody 263 (Mab263), a monoclonal antibody against the growth hormone receptor (GHR), acts as an agonist in vitro and in vivo. However, the intracellular signaling pathways triggered by Mab263 have not yet been delineated. Therefore, we examined the intracellular signaling pathways induced by Mab263 in vivo and in vitro in the present study. The results show that this antibody activated janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), STAT1 and extracellular signal-regulated kinase 1/2 (ERK1/2), but not STAT5. The phosphorylation kinetics of JAK2, STAT3/1 and ERK1/2 induced by Mab263 were subsequently analyzed in dose-response and time course experiments. Our observations indicate that Mab263 induced different intracellular signaling pathways than GH, which indicates that Mab263 is a signal-specific molecule and that Mab263 may be a valuable biological reagent to study the mechanism(s) of GHR-mediated intracellular signaling pathways.