Opposing roles of ERK and p38 MAP kinases in FGF2-induced astroglial process extension.
The stellate processes of astroglial cells undergo extensive remodeling in response to neural injury. Little is known about intracellular signaling mechanisms controlling process extension. We tested roles for the ERK and p38 MAP kinase pathways in a simplified culture model. FGF2-induced process extension was preceded by a strong and transient phosphorylation of ERK, and a modest activation of p38 MAP kinase, which exhibited significant basal activity. Phosphorylated ERK was found predominantly in the cytoplasm, whereas activated p38 MAP kinase was nuclear. Process extension was completely blocked by the specific MEK inhibitor U0126. Conversely, inhibition of the p38 MAP kinase pathway with SB202190 stimulated spontaneous process growth and greatly potentiated FGF2-induced process extension. The p38 inhibitor effect was reproduced with an adenovirus expressing dominant-negative p38 MAP kinase. Selective pharmacological blockade of MAP kinase pathways may enable modulation of the astroglial response to injury so as to promote neural regeneration.
Heffron
Daniel S
DS
Department of Pathology, University of Virginia Health System, PO Box 800904, Charlottesville, VA 22908, USA.
Mandell
James W
JW
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D049108:Cell Enlargement; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016548:Prosencephalon / Q000166:cytology / Q000201:enzymology; D020794:Receptor Protein-Tyrosine Kinases / Q000494:pharmacology*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D017468:Receptors, Fibroblast Growth Factor; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases