Inhibition of p42 and p44 mitogen-activated protein kinase activity by PD98059 does not suppress nerve growth factor-induced survival of sympathetic neurones.
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.
Virdee
K
K
Department of Biochemistry, University of Cambridge, England, U.K.
Tolkovsky
A M
AM
D000818:Animals; D000831:Animals, Newborn; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000201:enzymology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D009414:Nerve Growth Factors; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one