Artikel
Cell type-specific pattern of constitutive transcriptional activation of transcription factors by the G protein-coupled receptor Mas
Zelltyp-spezifisches Muster der konstitutiven transkriptionalen Aktivierung von Transkriptionsfaktoren durch den G-Protein gekoppelten Rezeptor Mas
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Autoren
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J. Zhang
- Charité Berlin, Campus Benjamin Franklin (CBF) (Berlin, D)
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F. Gembardt
- Charité Berlin, Campus Benjamin Franklin (CBF) (Berlin, D)
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Y. Wang
- Charité Berlin, Campus Benjamin Franklin (CBF) (Berlin, D)
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T. Walther
- Charité Berlin, Campus Benjamin Franklin (CBF) (Berlin, D)
| Veröffentlicht: | 8. August 2006 |
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Gliederung
Text
The Mas proto-oncogene encodes a G protein-coupled receptor and was identified due to its tumorigenic properties. Recently, we identified Angiotensin-(1-7) as a functional ligand for the receptor. Mas can also physically interact with the Angiotensin II receptor AT1. Furthermore, we showed that Mas constitutively activates the transcription factor, serum response element (SRE), in HEK293 cells.
To investigate, whether this effect is cell type-specific and whether other transcription factors are also activated by Mas, we tested the transcriptional activations of the nuclear factor of activated T-cells (NFAT), nuclear factor-kappaB (Nf kappa B), activator protein (AP1), and SRE, in different cell lines. HEK293, COS-1, and CHO cells were transiently co-transfected with pcDNA3.1RNMas, luciferase reporter plasmids (pNFAT-TA-Luc, pNF kappa B-TA-Luc, pAP1-TA-Luc, or pSRE-Luc) coding a firefly luciferase reporter gene driven by transcription factor-activating promoters, and pRLTK, which encodes a renilla lucifase used as internal control within the dual lucifease assay.
In all cell lines, Mas dose-dependently induced ligand independently the transcription of all four transcription factors. However, the levels of transcriptional activation in the three cell types were different. While the highest NFAT activation (9.4±0.6 fold) was detected in CHO cells, NF kappa B (3.2±0.2 fold), AP1 (5.0±0.7 fold), and SRE (295.4±63.1 fold) activation were measured highest in COS-1 cells. In contrast, the lowest NFAT (3.6±0.6 fold) and Nf kappa B (1.8±0.3 fold) activation were shown in HEK cells, and AP1 (2.5±0.1 fold) and SRE (7.2±1.1 fold) activation in CHO cells.
Our data demonstrates that Mas constitutively activates the transcription factors NFAT, NF kappa B, AP1, and SRE in all investigated cell types. Although the activation grades are cell type-specific, the results indicate a general mechanism of constitutive transcriptional control by the G protein-coupled receptor Mas on a variety of transcription factors.
