PMID- 16238696 OWN - NLM STAT- MEDLINE DCOM- 20060120 LR - 20131121 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 95 IP - 6 DP - 2005 Dec TI - Roles of extracellular signal-regulated kinase and Akt signaling in coordinating nuclear transcription factor-kappaB-dependent cell survival after serotonin 1A receptor activation. PG - 1653-66 AB - To investigate the functional consequences of cross-talk between multiple effectors of serotonin (5-HT) 1A receptor, we employed transfected Chinese hamster ovary cells. Activation of 5-HT 1A receptor stimulated extracellular signal-regulated kinase (ERK)1/2, Akt and nuclear transcription factor-kappaB (NF-kappaB). Stimulation of cells with 5-HT 1A receptor agonist induced a rapid but transient ERK1/2 phosphorylation followed by increased phosphorylation of Akt. Elevated Akt activity in turn suppressed Raf activity and induced a decline in ERK activation. The activation of ERK and Akt downstream of 5-HT 1A receptor was sensitive to inhibitors of Ras, Raf and phosphatidylinositol 3-kinase (PI3K). Stimulation of 5-HT 1A receptor also resulted in activation of NF-kappaB through a decrease in inhibitor of nuclear transcription factor-kappaB. In support of the importance of 5-HT 1A receptor signaling for cell survival, inhibition of NF-kappaB facilitated caspase 3 activation and cleavage of poly (ADP-ribose) polymerase, while treatment of cells with agonist inhibited caspase 3, DNA fragmentation and cell death. Both agonist-dependent NF-kappaB activation and cell survival were decreased by Akt Inhibitor II or by overexpression of dominant-negative Akt. These findings suggest a role for 5-HT 1A receptor signaling in the Ras/Raf-dependent regulation of multiple intracellular signaling pathways that include ERK and PI3K/Akt. Of these, only PI3K/Akt and NF-kappaB activation were required for 5-HT 1A receptor-dependent cell survival, implying that the relative distribution of signals between competing transduction pathways determines the functional outcome of 5-HT 1A receptor activation. FAU - Hsiung, Shu-chi AU - Hsiung SC AD - Division of Neuroscience, New York State Psychiatric Institute, New York, New York 10032, USA. FAU - Tamir, Hadassah AU - Tamir H FAU - Franke, Thomas F AU - Franke TF FAU - Liu, Kuo-peing AU - Liu KP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051020 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (NF-kappa B) RN - 0 (Piperazines) RN - 0 (Pyridines) RN - 0 (Serotonin Receptor Agonists) RN - 112692-38-3 (Receptor, Serotonin, 5-HT1A) RN - 71IH826FEG (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide) RN - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) RN - EC 2.4.2.31 (Pertussis Toxin) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) RN - I2ZWO3LS3M (Trypan Blue) SB - IM MH - 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology MH - Adenoviridae/genetics MH - Animals MH - Blotting, Western MH - CHO Cells MH - Caspase 3 MH - Caspases/metabolism MH - Cell Proliferation MH - Cell Survival/drug effects MH - Cricetinae MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/*physiology MH - Genetic Vectors MH - Humans MH - NF-kappa B/*physiology MH - Pertussis Toxin/pharmacology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation MH - Piperazines/pharmacology MH - Poly(ADP-ribose) Polymerases/metabolism MH - Proto-Oncogene Proteins c-akt/*physiology MH - Pyridines/pharmacology MH - Receptor, Serotonin, 5-HT1A/*drug effects MH - Serotonin Receptor Agonists/*pharmacology MH - Signal Transduction/*physiology MH - Trypan Blue EDAT- 2005/10/22 09:00 MHDA- 2006/01/21 09:00 CRDT- 2005/10/22 09:00 PHST- 2005/10/22 09:00 [pubmed] PHST- 2006/01/21 09:00 [medline] PHST- 2005/10/22 09:00 [entrez] AID - JNC3496 [pii] AID - 10.1111/j.1471-4159.2005.03496.x [doi] PST - ppublish SO - J Neurochem. 2005 Dec;95(6):1653-66. doi: 10.1111/j.1471-4159.2005.03496.x. Epub 2005 Oct 20.