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 current in vivo results are in concordance with our earlier in vitro finding that GMF promotes the activity of p38, and they implicate the participation of GMF in stress-induced catecholamine synthesis.
Zaheer
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A
Department of Neurology, University of Iowa College of Medicine, Iowa City 52242, USA.
Lim
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R
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000235:genetics; D005786:Gene Expression Regulation; D020904:Glia Maturation Factor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020904:Glia Maturation Factor; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D014446:Tyrosine 3-Monooxygenase; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2