Abstract
Apart from its high affinity receptor TrkA, nerve growth factor (NGF) can also stimulate the low affinity receptor p75(LNTR) and induce a Trk-independent signaling cascade. We examined the possible involvement of mitogen-activated protein kinase (MAPK) in this signaling pathway in neuronal cultures of the cerebellum of P2-aged rats and PCNA cells; both cell types express p75(LNTR) but not TrkA. We found a fast and transient phosphorylation of p42- and p44-MAPK after stimulation with NGF or C(2)-ceramide which proved to be sensitive to inhibition of MAPK kinase and protein kinase A (PKA). As stimulation with NGF also activated p21Ras it can be concluded that at least part of the observed MAPK activation was effected via p21Ras and via PKA.
MeSH terms
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Age Factors
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Animals
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Cells, Cultured
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / metabolism*
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Nerve Growth Factor / pharmacology*
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Neurons / drug effects
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Neurons / metabolism
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Oncogene Protein p21(ras) / metabolism
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Phosphorylation
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Rats
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Receptor, Nerve Growth Factor / drug effects*
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Receptor, Nerve Growth Factor / metabolism
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Sphingosine / analogs & derivatives
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Sphingosine / pharmacology
Substances
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Enzyme Inhibitors
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N-acetylsphingosine
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Receptor, Nerve Growth Factor
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Nerve Growth Factor
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase Kinases
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Oncogene Protein p21(ras)
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Sphingosine