NERVE GROWTH FACTOR-INDUCED DIFFERENTIATION IS NEUROBLASTOMA-CELLS EXPRESSING TRKA BUT LACKING P75(NGFR)

Nerve growth factor (NGF) binds to two distinct cell surface receptors , TrkA, which is a receptor tyrosine kinase, and p75(NGFR), whose role in NGF-induced signal transduction remains unclear. We have found tha t human neuroblastoma IMR-32 cells express TrkA, but p75(NGFR) express ion was not detectable in these cells by northern blot analysis, immun oblotting, or chemical crosslinking experiments. Despite the lack of p 75(NGFR) expression, subnanomolar concentrations of recombinant human NGF induced neurite outgrowth, tyrosine phosphorylation, and immediate early gene expression in these cells. These results strongly suggest that NGF-induced neuronal differentiation in IMR-32 cells is initiated through TrkA in the absence of p75(NGFR). Thus, IMR-32 cells may prov ide a model for studying neurotrophic effects of NGF on adult striatal cholinergic neurons, which also lack p75(NGFR) expression.