GSK3β modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner

Zhang, Weishi, Smith, Adam, Liu, Jun-ping, Cheung, Nam Sang, Zhou, Shufeng, Liu, Ke, Li, Qiu-Tian and Duan, Wei 2009, GSK3β modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner, Cellular signalling, vol. 21, no. 2, pp. 237-245.

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Title GSK3β modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner
Author(s) Zhang, Weishi
Smith, Adam
Liu, Jun-ping
Cheung, Nam Sang
Zhou, Shufeng
Liu, Ke
Li, Qiu-Tian
Duan, Wei
Journal name Cellular signalling
Volume number 21
Issue number 2
Start page 237
End page 245
Total pages 9
Publisher Elsevier Inc.
Place of publication Amsterdam, The Netherlands
Publication date 2009-02
ISSN 0898-6568
1873-3913
Keyword(s) PACAP
GSK3β
rap1
vaveolae
PC12
neurite outgrowth
Summary 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 GSK3β is a novel modulator in PACAP signalling. PACAP induces phosphorylation of serine 9 in GSK3β, which is inhibited by silencing Rap1. Lithium and valproate promote but wortmannin and LY294002 attenuate PACAP-induced phosphorylation of both GSK3β and ERK1/2, whereas MEK inhibitor PD98059 inhibits nerve growth factor- but not PACAP-induced phosphorylation of GSK3β, suggesting that GSK3β operates downstream of Rapt 1 but upstream of ERK1/2 in PACAP signalling. Inhibition or stimulation of GSK3β 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 GSK3β is a critical regulator in PACAP-induced neuronal differentiation.
Language eng
Field of Research 111201 Cancer Cell Biology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
HERDC collection year 2009
Copyright notice ©2008, Elsevier Inc
Persistent URL http://hdl.handle.net/10536/DRO/DU:30019538

Document type: Journal Article
Collection: School of Medicine
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Created: Wed, 16 Sep 2009, 15:04:26 EST by Deborah Wittahatchy

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