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GSK3ß modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner
Citation
Zhang, W and Smith, A and Liu, J and Cheung, NS and Zhou, S and Liu, K and Li, QT and Duan, W, GSK3s modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner, Cellular Signalling, 21, (2) pp. 237-245. ISSN 0898-6568 (2009) [Refereed Article]
DOI: doi:10.1016/j.cellsig.2008.10.008
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neurotrophic peptide. Here, we show that PACAP recruits Rap1 into caveolin-enriched membrane subdomains in PC12 cells and activates Rap1, nuclear ERK1/2, Elk-1 and CREB in a caveolae-dependent manner. We reveal that GSK3ß is a novel modulator in
PACAP signalling. PACAP induces phosphorylation of serine 9 in GSK3ß, which is inhibited by silencing Rap1. Lithium and valproate promote but wortmannin and LY294002 attenuate PACAP-induced phosphorylation of both GSK3ß and ERK1/2, whereas MEK inhibitor PD98059 inhibits nerve growth factor- but not PACAPinduced phosphorylation of GSK3ß, suggesting that GSK3ß operates downstream of Rapt 1 but upstream of ERK1/2 in PACAP signalling. Inhibition or stimulation of GSK3ß results in a 2-fold increase and 6-fold decrease in PACAP-induced neurite outgrowth, respectively. These results reveal an important role of
caveolae in the signal transduction of PACAP and that GSK3ß is a critical regulator in PACAP-induced neuronal differentiation.
Item Details
Item Type: | Refereed Article |
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Keywords: | PACAP, GSK3ß, Rap1, Caveolae, PC12, Neurite outgrowth |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Neurosciences |
Research Field: | Cellular nervous system |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Cheung, NS (Dr Nam Cheung) |
ID Code: | 59003 |
Year Published: | 2009 |
Web of Science® Times Cited: | 18 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2009-11-12 |
Last Modified: | 2011-07-28 |
Downloads: | 0 |
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