Journal article
Interaction between ERK and GSK3β Mediates Basic Fibroblast Growth Factor-induced Apoptosis in SK-N-MC Neuroblastoma Cells
The Journal of biological chemistry, Vol.283(14), pp.9248-9256
04/04/2008
DOI: 10.1074/jbc.M707316200
PMCID: PMC2431019
PMID: 18263590
Abstract
The Ewing's sarcoma family of tumors (ESFT) includes Ewing's sarcoma (ES),
Askin's tumor of the chest wall, and peripheral primitive neuroectodermal
tumor. Basic fibroblast growth factor (FGF2) suppresses the growth of ESFT
cells and causes their apoptosis. The underlying mechanism is unclear. Using a
human peripheral primitive neuroectodermal tumor cell line, SK-N-MC, we
demonstrated FGF2 stimulated phosphorylation of ERK1 and ERK2 (pERK1/2) and
GSK3β (pGSK3β(Tyr-216)), all of which were primarily retained in the
cytoplasm. FGF2 promoted the association between ERK and pGSK3β(Tyr-216).
Inhibitors for GSK3β (TDZD and LiCl) and ERK (PD98059) protected cells
from FGF2-induced apoptosis. On the other hand, inhibitors of GSK3β, but
not PD98059 decreased ERK/pGSK3β(Tyr-216) association and caused a
nuclear translocation of pERK1/2. Similarly, expression of a kinase-deficient
(K85R) GSK3β or GSK3β-small interfering RNA inhibited FGF2-regulated
ERK/pGSK3β(Tyr-216) association and translocated pERK to the nucleus.
Both K85R GSK3β and small interfering RNA offered protection against
FGF2-induced cell death. In contrast, overexpression of wild-type GSK3β
sensitized cells to FGF2 cytotoxicity. Hydrogen peroxide and ethanol enhanced
FGF2-stimulated pGSK3β(Tyr-216), ERK/pGSK3β(Tyr-216) association,
and cytoplasmic retention of pERK1/2. As a result, they potentiated
FGF2-induced cell death. Taken together, our results suggested that
FGF2-induced accumulation of pERK1/2 in the cytoplasm is toxic for SK-N-MC
cells. The formation of an ERK·GSK3β complex retained pERK1/2 in
the cytoplasm. In contrast, disruption of the ERK·GSK3β complex
resulted in nuclear translocation of pERK1/2 and offered protection.
Details
- Title: Subtitle
- Interaction between ERK and GSK3β Mediates Basic Fibroblast Growth Factor-induced Apoptosis in SK-N-MC Neuroblastoma Cells
- Creators
- Cuiling Ma - West Virginia UniversityKimberly A Bower - West Virginia UniversityGang Chen - West Virginia UniversityXianglin Shi - University of KentuckyZun-Ji Ke - West Virginia UniversityJia Luo - West Virginia University
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.283(14), pp.9248-9256
- DOI
- 10.1074/jbc.M707316200
- PMID
- 18263590
- PMCID
- PMC2431019
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology
- Language
- English
- Date published
- 04/04/2008
- Academic Unit
- Pathology
- Record Identifier
- 9984201120002771
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