In the present study, we have shown that KCl known as an inducer for differentiation of neuronal cells increases the human Sia-alpha2,3-Gal-beta1,4-GlcNAc-R:alpha2,8-sialyltransferase (hST8Sia III) gene transcription via phosphoinositide 3 kinase (PI-3K) in glioblastoma U-87MG cells. The induction of hST8Sia III by KCl is regulated at the transcriptional level in a dose- and time-dependent manner as evidenced by reverse transcription-polymerase chain reaction (RT-PCR). To elucidate the mechanism underlying the regulation of hST8Sia III gene expression in U-87MG cells induced by KCl, we characterized the promoter region of the hST8Sia III gene. Functional analysis of the 5'-flanking region of the hST8Sia III gene by the transient expression method showed that the -1194 to -816 region functions as the KCl-inducible promoter in U-87MG cells. Furthermore, as evidenced by Western blot analysis and RT-PCR, KCl-induced expression of hST8Sia III gene was dependent on the PI-3K signal transduction pathway during the neuronal differentiation of U-87 cells, as an increase in beta-tubulin III known as a neuronal differentiation marker was observed. In KCl-depolarization on U-87 cells, the PI-3K-dependent promoter activation at the -1194 to -816 region up-regulated expression of hST8Sia III gene. These results suggest that the expression of hST8Sia III gene via the PI-3K signaling pathway is enhanced during KCl-induced differentiation of U-87 cells by increasing expression of beta-tubulin III.