Home
Resources
Publications
Roles of Extracellular Signal-Regulated Kinase and Akt Signaling in Coordinating Nuclear Transcription factor-kappaB-dependent Cell Survival After Serotonin 1A Receptor Activation

Roles of Extracellular Signal-Regulated Kinase and Akt Signaling in Coordinating Nuclear Transcription factor-kappaB-dependent Cell Survival After Serotonin 1A Receptor Activation

Shu-chi Hsiung, Hadassah Tamir, Thomas F Franke, Kuo-peing Liu

J Neurochem. 2005 Dec;95(6):1653-66.

PMID: 16238696

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415211	Akt Inhibitor II			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: