COX-2 promoter activation by AT1R-Gq-PAK-p38β signaling in intestinal epithelial cells
| Autor: | Hung Pham, Romina Vincenti, Lee W. Slice |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
MAP Kinase Signaling System
Pyridines Biophysics Heterologous MAP Kinase Kinase 6 Biology CREB Biochemistry Gene Expression Regulation Enzymologic Receptor Angiotensin Type 1 Cell Line Mitogen-Activated Protein Kinase 11 Structural Biology Transcription (biology) Genetics Animals Enzyme Inhibitors Intestinal Mucosa Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Receptor Molecular Biology Flavonoids Regulation of gene expression Angiotensin II Imidazoles Epithelial Cells Promoter Molecular biology Rats Intestines p21-Activated Kinases Cyclooxygenase 2 Cell culture biology.protein GTP-Binding Protein alpha Subunits Gq-G11 Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1779:408-413 |
| ISSN: | 1874-9399 |
| DOI: | 10.1016/j.bbagrm.2008.05.004 |
| Popis: | Cyclooxygenase-2 (COX-2) is rapidly induced by angiotensin (Ang)-II in the non-tumorigenic, rat intestinal epithelial cell line, IEC-18, through its G-protein coupled receptor, AT1R. Here, we investigate the ability of Ang II to regulate transcription of the COX-2 promoter and a Gal4-CREB heterologous promoter in IEC-18 cells. Ang II and EGF induced similar levels of transcription from the COX-2 and Gal4-CREB promoters. Over-expression of constitutively active Galpha proteins q, 11, 12 and 13, showed induction by GalphaqQ209L and by Galpha11Q209L for both the COX-2 and Gal4-CREB promoters. Co-expression of RGS 2, 3 or 4 but not the RGS domain of p115RhoGEF inhibited Ang II-dependent induction of the COX-2 and Gal4-CREB promoters. Expression of constitutively active MKK6 EE but not MKK3 EE induced the COX-2 and Gal4-CREB promoters via p38MAPK. SB202190 but not PD98059 inhibited induction of the COX-2 promoter by over-expression of the constitutively active PAK1T423E. Expression of the kinase-inactive PAK1K299R inhibited both Ang II-dependent induction of the COX-2 promoter and induction of the COX-2 and Gal4-CREB promoters by GalphaqQ209L. These data demonstrate that in IEC-18 cells, Ang II-dependent activation of the COX-2 promoter is mediated primarily through Gq/11 signaling via a PAK/MKK6/p38beta/CREB signaling cascade. |
| Databáze: | OpenAIRE |
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