Nerve growth factor-stimulated mitogen-activated protein kinase activity is not necessary for neurite outgrowth of chick dorsal root ganglion sensory and sympathetic neurons.
Nerve growth factor (NGF)-stimulated neurite outgrowth in the rat PC12 tumor cell line recently has been shown to depend on the activation of the mitogen-activated protein (MAP) kinase kinase 1 (MEK1) (Pang et al.: J Biol Chem 270:13585-13588, 1995). In this study we have analyzed whether or not function of the MAP kinase pathway is necessary for NGF-stimulated neurite outgrowth in two subtypes of primary neurons derived from the embryonic chick peripheral nervous system (PNS). Treatment of p21ras-dependent dorsal root ganglion (DRG) sensory neurons (E9) with the MEK1 inhibitor PD98059 at concentrations up to 100 microM did not prevent NGF-stimulated neurite outgrowth. At this concentration NGF-stimulated tyrosine phosphorylation of MAP kinase p42 as well as MAP kinase activity both were decreased by approximately 80%. Essentially the same results were obtained with p21ras-independent sympathetic neurons (E12). We conclude that, in contrast to the PC12 tumor cell line, NGF-stimulated MAP kinase activity is not necessary for neurite outgrowth of DRG sensory and sympathetic neurons derived from the chick PNS.
Klinz
F J
FJ
Department of Molecular Neurobiochemistry, Ruhr-Universität Bochum, Germany.
Wolff
P
P
Heumann
R
R
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology*; D005728:Ganglia, Sympathetic / Q000166:cytology*; D048369:MAP Kinase Kinase 1; D008297:Male; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D008934:Mitogens / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000166:cytology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D004791:Enzyme Inhibitors; D005419:Flavonoids; D008934:Mitogens; D009414:Nerve Growth Factors; D047428:Protein Kinase Inhibitors; D014443:Tyrosine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one