Protein Kinase C#alpha# Isoform Regulates the Activation of the MAP Kinase ERK1/2 in Human Glioma Cells: Involvement in Cell Survival and Gene Expression

摘要

Protein kinase C is a family of serine/threonine pro- tein kinases involved in many cellular responses, includ- ing cell survival and apoptosis. We have recently found that specific inhibition of the PKCa isoform by nucleic acid enzymes induced apoptosis in sensitive cells. Here we show that in PKCa DNA enzyme-treated glioma cells the activation of MAP kinases ERKl/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 calphos- tin, a specific inhibitor for PKC. These results would indicate that the ERKl/2 signaling pathway plays an important role in glioma cell survival and that the PKCa isoform is the main modulator of this pathway. Further- more, we show that the ERK1/2 signaling pathway is required for the constitutive expression of the basic fi- broblast growth factor, a potent mitogen for glioma cell growth.