Journal article
The role of epidermal growth factor receptor in ethanol-mediated inhibition of activator protein-1 transactivation
Biochemical pharmacology, Vol.69(12), pp.1785-1794
2005
DOI: 10.1016/j.bcp.2005.03.029
PMID: 15878157
Abstract
A potential mechanism underlying ethanol-induced alterations in gene expression is the disruption of transcription factor activity. Growth factor receptors, particularly receptor tyrosine kinases, play an important role in modulating many biological effects of ethanol. We demonstrated here that the expression of epidermal growth factor receptor (EGFR) mediated the effect of ethanol on the activity of transcription factor activator protein-1 (AP-1). Ethanol had little effect on AP-1 activity in the fibroblast cells devoid of EGFR (B82); however, it significantly suppressed AP-1 activity in B82 cells that were stably transfected with either a wild-type EGFR (B82L) or a kinase-deficient receptor (B82M721) in a concentration-dependent manner. EGF activated AP-1 only in B82L cells; the activation was mediated primarily by Akt and ERK. Ethanol inhibited EGF-induced EGFR autophosphorylation, phosphorylation of ERK as well as Akt and its substrate GSK-3β, and subsequently blocked EGF-stimulated AP-1 activation in B82L cells. On the other hand, ethanol had little effect on EGF-stimulated JNK activation. Phorbol ester 12-
O-teradecanoyl-phorbol-13-acetate (TPA) activated AP-1 in B82L and B82M721 cells, but not B82 cells. TPA-induced activation of ERK and PKCδ was dependent on the expression of EGFR although the intrinsic kinase activity of EGFR was not required. In contrast, TPA-induced phosphorylation of p38 MAPK, JNKs and other PKC isoforms was independent of EGFR. Ethanol selectively inhibited TPA-induced phosphorylation of ERK and PKCδ, and modestly suppressed TPA-stimulated AP-1 activation in B82L and B82M721 cells. Thus, EGFR plays a critical role in the interaction between ethanol and AP-1.
Details
- Title: Subtitle
- The role of epidermal growth factor receptor in ethanol-mediated inhibition of activator protein-1 transactivation
- Creators
- Cuiling Ma - West Virginia UniversityKimberly A Bower - West Virginia UniversityHong Lin - West Virginia UniversityGang Chen - West Virginia UniversityChuanshu Huang - York UniversityXianglin Shi - York UniversityJia Luo - West Virginia University
- Resource Type
- Journal article
- Publication Details
- Biochemical pharmacology, Vol.69(12), pp.1785-1794
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.bcp.2005.03.029
- PMID
- 15878157
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Language
- English
- Date published
- 2005
- Academic Unit
- Pathology
- Record Identifier
- 9984186531202771
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