Neurite outgrowth is a central event of neuronal differentiation that proceeds in multiple processes requiring various cellular factors. Here we demonstrated that c-Jun N-terminal kinase I (JNKI) plays an essential role in RA-induced neurite outgrowth of SH-SY5Y cells. Treatment of SH-SY5Y cells with RA induced a strong activation of JNKI within 10 min, and the immediate increase of JNKI activity returned to the basal level in an hour. The second surge of JNKI activity was observed around I day after RA treatment, which coincided with the period of extensive neurite outgrowth. Interestingly, phospho-JNK was concentrated in the nucleus of cells during the early induction, whereas it was distributed into neurite processes during the delayed second activation period. In SH-SY5Y carrying a dominant negative form of SEKI, an upstream kinase of JNKI, both early and late inductions of JNKI activity were repressed along with RA-induced neurite outgrowth. These results suggest that JNKI plays an essential role in RA-induced neuronal differentiation of SH-SY5Y cells.
- Neuronal differentiation