Survival of cultured cerebellar granule neurons can be maintained by Akt-dependent and Akt-independent signaling pathways.
Cerebellar granule neurons can be maintained in culture by four factors: depolarizing levels of potassium (HK, 25 mM), cyclic AMP elevating agents and analogs (cyclic adenosine monophosphate, cAMP), insulin-like growth factor-1 (IGF-1), or lithium. We investigated the possibility that the signal transduction pathways utilized by these four survival factors might converge at a common molecular target and that the serine/threonine kinase Akt might be the convergent molecule. Previous research demonstrated that the four factors could phosphorylate and activate Akt; thus, using pharmacological inhibition of Akt and overexpression of an adenoviral delivered dominant negative Akt construct, we analyzed the role of Akt in the survival mediated by each factor. We found that although Akt is required for the survival mediated by IGF-1 and lithium, it is dispensable for the survival mediated by high potassium and cAMP.
Department of Molecular and Cell Biology, University of Texas at Dallas, 2601 N. Floyd Road, Richardson, TX 75083, USA.
Paul C
PC
Chin
Santosh R
SR
D'Mello
D000818:Animals; D000831:Animals, Newborn; D001381:Azepines / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
D001381:Azepines; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; C056218:ML 9; D007334:Insulin-Like Growth Factor I; D008094:Lithium; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt