title: Activated phosphatidylinositol 3-kinase and Akt kinase promote survival of superior cervical neurons.
abstract: The signaling pathways that mediate the ability of NGF to support survival of dependent neurons are not yet completely clear. However previous work has shown that the c-Jun pathway is activated after NGF withdrawal, and blocking this pathway blocks neuronal cell death. In this paper we show that over-expression in sympathetic neurons of phosphatidylinositol (PI) 3-kinase or its downstream effector Akt kinase blocks cell death after NGF withdrawal, in spite of the fact that the c-Jun pathway is activated. Yet, neither the PI 3-kinase inhibitor LY294002 nor a dominant negative PI 3-kinase cause sympathetic neurons to die if they are maintained in NGF. Thus, although NGF may regulate multiple pathways involved in neuronal survival, stimulation of the PI 3-kinase pathway is sufficient to allow cells to survive in the absence of this factor.
authors.affiliation: Eisai London Research Laboratories Ltd., Bernard Katz Building, University College London, London WC1E 6BT, United Kingdom.
authors.forename: K L
authors.initials: KL
authors.lastname: Philpott
authors.forename: M J
authors.initials: MJ
authors.lastname: McCarthy
authors.forename: A
authors.initials: A
authors.lastname: Klippel
authors.forename: L L
authors.initials: LL
authors.lastname: Rubin
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D009414:Nerve Growth Factors / Q000172:deficiency / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*
chemical_list: D009414:Nerve Growth Factors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D016755:Proto-Oncogene Proteins c-jun; C494920:Akt1 protein, rat