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(Received for publication, March 12, 1996, and in revised form, May 28, 1996)
,§
and
From the Departments of Components of the mitogen-activated protein
kinase (MAP kinase) signaling pathway, including Ras, Raf, and MAP
kinase, are necessary for nerve growth factor (NGF)-induced neurite
outgrowth in PC12 cells. We have investigated the role of this pathway
in promoting survival of primary sympathetic neurons that die when
deprived of NGF. NGF caused rapid and sustained increases
(approximately 4-fold) in the activities of the ERK-1 and ERK-2
isoforms of MAP kinase. PD 098059, an inhibitor of MAP kinase kinase
activation, blocked the effects of NGF on both kinase isoforms.
However, PD 098059 did not attenuate the effects of NGF on neuronal
survival. In addition, MAP kinase activity was not increased by
chlorophenylthio-cAMP, a cell-permeable analog of cAMP that supports
neuronal survival in the absence of NGF. These findings indicate that
activation of MAP kinase is not required for the actions of either cAMP
or NGF on neuronal survival.
Molecular Biology and
Pharmacology and § Neurology, Washington University School
of Medicine, St. Louis, Missouri 63110
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