Inhibition of p42 and p44 mitogen-activated protein kinase activity by PD48059 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.
机构:
Mayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Ctr Basic Res Digest Dis, Rochester, MN 55905 USAMayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Ctr Basic Res Digest Dis, Rochester, MN 55905 USA
Park, J
Gores, GJ
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Mayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Ctr Basic Res Digest Dis, Rochester, MN 55905 USAMayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Ctr Basic Res Digest Dis, Rochester, MN 55905 USA
Gores, GJ
Patel, T
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Mayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Ctr Basic Res Digest Dis, Rochester, MN 55905 USAMayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Ctr Basic Res Digest Dis, Rochester, MN 55905 USA