The hyperresponsiveness of cells expressing truncated erythropoietin receptors is contingent on insulin-like growth factor-1 in fetal calf serum.

摘要: We demonstrate herein that the well documented hyperresponsiveness to erythropoietin (Epo) of Ba/F3 cells expressing C-terminal truncated receptors (EpoRs) is contingent on these being in fetal calf serum (FCS). In absence FCS, their Epo-induced proliferation far poorer than wild-type (WT) EpoRs. This hyporesponsiveness also seen DA-3 fact, long-term studies performed show even at saturating concentrations Epo, die via apoptosis, while bearing WT EpoRs do not, and this programmed cell death correlates with an inability Epo-stimulated induce tyrosine phosphorylation MAPK activation p70S6K. Using neutralizing antibodies insulin-like growth factor (IGF)-1, we a major non-Epo FCS contributes hyperresponsive phenotype IGF-1. Our results suggest Epo-hypersensitivity EpoR due combined effects not possessing binding site for negative regulator, SHP-1, triggering proliferation-inducing/apoptosis-inhibiting cascades, lost through truncation, by