Protein kinase Calpha isoform regulates the activation of the MAP kinase ERK1/2 in human glioma cells: involvement in cell survival and gene expression.
Protein kinase C is a family of serine/threonine protein kinases involved in many cellular responses, including cell survival and apoptosis. We have recently found that specific inhibition of the PKCalpha isoform by nucleic acid enzymes induced apoptosis in sensitive cells. Here we show that in PKCalpha DNA enzyme-treated glioma cells the activation of MAP kinases ERK1/2 is inhibited, whereas their total level was not significantly affected by the treatment. Similar results were obtained when the overall activity of the PKC was inhibited by calphostin, a specific inhibitor for PKC. These results would indicate that the ERK1/2 signaling pathway plays an important role in glioma cell survival and that the PKCalpha isoform is the main modulator of this pathway. Furthermore, we show that the ERK1/2 signaling pathway is required for the constitutive expression of the basic fibroblast growth factor, a potent mitogen for glioma cell growth.
Leirdal
M
M
Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.
Sioud
M
M
D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000201:enzymology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051571:Protein Kinase C-alpha; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D009281:Naphthalenes; C061465:calphostin complex; D016222:Fibroblast Growth Factor 2; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one