INVOLVEMENT OF A CERAMIDE ACTIVATED PROTEIN PHOSPHATASE IN THE DIFFERENTIATION OF NEUROBLASTOMA NEURO2A CELLS

The possible involvement of protein phosphatase in ceramide-mediated n eural cell differentiation was investigated. Neuroblastoma Neuro2a cel l differentiation induced by retinoic acid, or conditions causing an i ncrease in cellular ceramide, was significantly inhibited by the serin e/threonine phosphatase inhibitor okadaic acid, at concentrations as l ow as 2.5 nM. A crude cytosolic preparation from Neuro2a cells was fou nd to have a cation-independent protein phosphatase activity that was stimulated by ceramide in a dose-dependent manner. Short- and long-cha in ceramides, but not sphingosine and related dihydro-derivatives, wer e active. Ceramide-activated protein phosphatase activity from Neuro2a cells was inhibited by 5 nM okadaic acid. The data indicate that a ty pe 2A protein phosphatase is involved in ceramide-mediated differentia tion of Neuro2a cells. (C) 1997 Federation of European Biochemical Soc ieties.