Aurintricarboxylic acid (ATA) has been reported to protect PC12 cells and cultured neuronal cells from serum starvation-induced cell death, and hippocampal neurons from N-methyl D-aspartate- or ischemia-induced cell death in vivo. We have found that ATA activated tyrosine phosphorylation cascade in PC12 cells as growth factors. Here, we report that ATA prevents cell death under serum starvation and induces tyrosine phosphorylation also in human neuroblastoma SH-SY5Y cells. Furthermore, it was found that erbB4, a member of epidermal growth factor receptor family, is tyrosine-phosphorylated in response to ATA. Both, erbB4 and its ligand, neu differentiation factor (NDF)/ heregulin family, have been reported to be expressed abundantly in nervous system. Thus, tyrosine phosphorylation of erbB4 might explain the neuro-protective activity of ATA.