p63RhoGEF - a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells
The purpose of our study was to investigate the role of endogenous p63RhoGEF in Gq/n-dependent RhoA activation and signaling in rat aortic smooth muscle cells (RASMCs). Therefore, we studied the expression and subcellular localization in freshly isolated RASMCs and performed loss of function experim...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 2010
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| In: |
The FASEB journal
Year: 2010, Volume: 24, Issue: 12, Pages: 4865-4876 |
| ISSN: | 1530-6860 |
| DOI: | 10.1096/fj.10.155499 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1096/fj.10.155499 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1096/fj.10.155499 
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| Author Notes: | Christina M. Wuertz, Akos Lorincz, Christiane Vettel, Martin A. Thomas, Thomas Wieland, and Susanne Lutz |
| Summary: | The purpose of our study was to investigate the role of endogenous p63RhoGEF in Gq/n-dependent RhoA activation and signaling in rat aortic smooth muscle cells (RASMCs). Therefore, we studied the expression and subcellular localization in freshly isolated RASMCs and performed loss of function experiments to analyze its contribution to RhoGTPase activation and functional responses such as proliferation and contraction. By this, we could show that p63RhoGEF is endogenously expressed in RASMCs and acts there as the dominant mediator of the fast angiotensin II (ANG II)-dependent but not of the sphingosine-1-phosphate (SjP)-dependent RhoA activation. p63RhoGEF is not an activator of the concomitant Rac1 activation and functions independently of caveo-lae. The knockdown of endogenous p63RhoGEF significantly reduced the mitogenic response of ANG II, abolished ANG II-induced stress fiber formation and cell elongation in 2-D culture, and impaired the ANG II-driven contraction in a collagen-based 3-D model. In conclusion, our data provide for the first time evidence that p63RhoGEF is an important mediator of ANG II-dependent RhoA activation in RASMCs and therewith a leading actor in the subsequently triggered cellular processes, such as proliferation and contraction.—Wuertz, C. M., Lorincz, A., Vettel, C., Thomas, M. A., Wieland, T., Lutz, S. p63RhoGEF—a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells. FASEB J. 24, 4865-4876 (2010). www.fasebj.org |
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| Item Description: | First published: 25 August 2010 Gesehen am 30.04.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1530-6860 |
| DOI: | 10.1096/fj.10.155499 |