Mitogen-activated protein kinase-independent pathways mediate the effects of nerve growth factor and cAMP on neuronal survival

Douglas J. Creedon, Eugene M. Johnson, John C. Lawrence

Research output: Contribution to journalArticle

169 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)20713-20718
Number of pages6
JournalJournal of Biological Chemistry
Issue number34
StatePublished - 1996
Externally publishedYes


ASJC Scopus subject areas

  • Biochemistry

Cite this