File(s) under permanent embargo
GSK3β modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner
journal contribution
posted on 2009-02-01, 00:00 authored by W Zhang, Adam Smith, J P Liu, Steve Cheung, S Zhou, K Liu, Q T Li, Wei DuanWei DuanPituitary 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.
History
Journal
Cellular signallingVolume
21Issue
2Pagination
237 - 245Publisher
Elsevier Inc.Location
Amsterdam, The NetherlandsPublisher DOI
ISSN
0898-6568eISSN
1873-3913Language
engPublication classification
C1 Refereed article in a scholarly journal; C Journal articleCopyright notice
2008, Elsevier IncUsage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC