Inhibition of p42 and p44 Mitogen-Activated Protein Kinase Activity by PD98059 Does Not Suppress Nerve Growth Factor-Induced Survival of Sympathetic Neurones |
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Authors: | Kanwar Virdee Aviva M Tolkovsky |
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Institution: | Department of Biochemistry, University of Cambridge, Cambridge, England |
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Abstract: | Abstract: Nerve growth factor (NGF) induces persistent p42 and p44 mitogen-activated protein kinase (MAPK) activity in sympathetic neurones in parallel to its survival-promoting activity. To investigate whether these MAPK activities are necessary for NGF-induced survival, we have inhibited NGF-stimulated p42/p44 MAPK activity over extended periods using the compound 2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059). Despite attaining up to 95% inhibition of p42/p44 MAPK activity in cultures treated with NGF and PD98059, neuronal survival is maintained undiminished, although a decrease in the density of the neuritic network is observed. Because p21Ras activity is essential for NGF-induced survival, we conclude that p21Ras-linked activities other than p42 and p44 MAPKs are responsible for mediating NGF-dependent survival of rat sympathetic neurones. |
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Keywords: | Cell death Apoptosis p21Ras Ciliary neurotrophic factor Leukemia inhibitory factor Cyclic AMP |
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