Nuclear translocation of p90 Rsk and phosphorylation of CREB is induced by ionomycin in a Ras-independent manner in PC12 cells

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Abstract
In the present study we examined the possible role of p90Rsk in pathways leading to neuronal differentiationud of PC12 cells induced by nerve growth factor (NGF) and the calcium ionophore ionomycin. PC12-ud M17 cells, expressing a dominant inhibitory Ras protein, do not undergo neuronal differentiation inud response to NGF like wild-type PC12 cells, but exhibit neurite outgrowth when treated with NGF in combinationud with ionomycin. However, the blockade of Ras in these cells results in failure of activation ofud mitogen-activated protein kinase (MAPK)/extracellular signal regulation kinase (ERK) (MEK) and ERKud activation as well, therefore kinases other than those of the ERK pathway might play a role in the inductionud of neuronal differentiation in this case. Here we show that p90Rsk translocates to the nucleus inud response to ionomycin in both wild-type PC12 and PC12-M17 cells, and this spatial distribution is followedud by increased phosphorylation of the cAMP response element binding protein (CREB). Sinceud CREB is believed to be the transcription factor that can integrate Ca2+, growth factor and cAMP-inducedud signals, we suggest that p90Rsk may be one of the kinases which is able to replace ERKs under certainud circumstances, thereby participating in Ras-independent neuronal differentiation induced by NGF plusud ionomycin