Glucophosphoisomerase (GPI), a glycolytic
enzyme, was recently described to share 90% sequence homology with
neuroleukin, a recently discovered
growth factor which promotes motor neuron regeneration in vivo, survival of peripheral and central neurons in vitro, and affects B cell
immunoglobulin synthesis. Interestingly,
neuroleukin activity was described to be antagonized by the human immunodeficiency virus (HIV-1) envelope
glycoprotein (gp120), with which
neuroleukin was found to share partial sequence homology. In this study, reduced GPI demonstrated similar activity to
neuroleukin in a novel bioassay using human and rat
neuroblastoma cell lines. In the presence of reduced GPI, these cells were found to differentiate, in terms of enhanced neurite extension at a reduced proliferation rate. These results demonstrate the existence of a novel
growth factor activity of an evolutionary ancient
enzyme. The nonreduced commercial form of GPI, probably the dimer, was found to be inactive in this bioassay. Using the
neuroblastoma cells model system, we further investigated the significance of the region of homology to HIV-1 envelope
glycoprotein (gp120) as the putative binding site of GPI to its receptor on neuronal cells.