Involvement of a ceramide activated protein phosphatase in the differentiation of neuroblastoma Neuro2a cells.
The possible involvement of protein phosphatase in ceramide-mediated neural cell differentiation was investigated. Neuroblastoma Neuro2a cell differentiation induced by retinoic acid, or conditions causing an increase in cellular ceramide, was significantly inhibited by the serine/threonine phosphatase inhibitor okadaic acid, at concentrations as low as 2.5 nM. A crude cytosolic preparation from Neuro2a cells was found to have a cation-independent protein phosphatase activity that was stimulated by ceramide in a dose-dependent manner. Short- and long-chain ceramides, but not sphingosine and related dihydro-derivatives, were active. Ceramide-activated protein phosphatase activity from Neuro2a cells was inhibited by 5 nM okadaic acid. The data indicate that a type 2A protein phosphatase is involved in ceramide-mediated differentiation of Neuro2a cells.
Prinetti
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A
Study Center for the Functional Biochemistry of Brain Lipids, Department of Medical Chemistry and Biochemistry, The Medical Faculty, University of Milan, Italy.
Bassi
R
R
Riboni
L
L
Tettamanti
G
G
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002518:Ceramides; D019319:Okadaic Acid; D014212:Tretinoin; D010749:Phosphoprotein Phosphatases; D013110:Sphingosine