The activation and nuclear translocation of extracellular signal-regulated kinases (ERK-1 and -2) appear not to be required for elongation of neurites in PC12D cells.

The outgrowth of neurites was induced in PC12D cells, a subline of PC12 cells, that were treated not only with NGF but also with dbcAMP, staurosporine or bFGF. Simultaneous activation and rapid nuclear translocation of MAP kinases (ERK-1 and ERK-2) were observed in cells treated with NGF or bFGF. But staurosporine and dbcAMP induced no or only slight activation of the kinases. The nuclear translocation of the MAP kinases was not induced by the latter agents. These observations suggest a close relationship between the activation and the nuclear translocation of MAP kinases and, moreover, that stimulation and relocalization of MAP kinases might not be required for the outgrowth of neurites from PC12D cells. Staurosporine and dbcAMP may stimulate a down-stream step of the NGF pathway, or a parallel pathway(s) to the MAP kinase cascade in promoting neurite formation from PC12D cells. These agents mimic the effects of NGF in promoting neurite outgrowth in cultured sympathetic neurons, but not in conventional PC12 cells. Because of the similarity between PC12D cells and primed cells, it seems possible that activation and nuclear translocation of MAP kinases might be required for the transcription-dependent differentiation step but might not be necessary for the elongation of neurites at least in response to staurosporine or to dbcAMP.