Overexpression of Glia Maturation Factor (GMF) in PC12 Pheochromocytoma Cells Activates p38 MAP Kinase, MAPKAP Kinase-2, and Tyrosine Hydroxylase

In order to study the intracellular regulatory function of glia maturation factor (GMF) in neuronal cells, we achieved a 10-fold overexpression of GMF in the rat pheochromocytoma cell line PC12 by infection with a replication-defective human adenovirus carrying a rat GMF cDNA insert. These cells showed a 3.6-fold increase in the activity of p38 MAP kinase, a 3.8-fold increase in the activity of MAPKAP-K2 (MAP kinase-activated protein kinase 2), and a 4.2-fold increase in the activity of tyrosine hydroxylase (TH). We also detected an increase in the phosphorylation of TH and the 25-kDa heat shock protein (Hsp25) without a concomitant increase in their corresponding protein levels, suggesting a posttranslational modification. It was previously established that in PC12 cells, MAPKAP-K2 is an immediate target of p38, and both TH and Hsp25 are immediate targets of MAPKAP-K2. The currentin vivoresults are in concordance with our earlierin vitrofinding that GMF promotes the activity of p38, and they implicate the participation of GMF in stress-induced catecholamine synthesis.