| Autor: |
Hansen, Jakob L, Hansen, Jonas T, Speerschneider, Tobias, Lyngsø, Christina, Erikstrup, Niels, Burstein, Ethan S, Weiner, David M, Walther, Thomas, Makita, Noriko, Iiri, Taroh, Merten, Nicole, Kostenis, Evi, Sheikh, Søren P |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Zdroj: |
Hansen, J L, Hansen, J T, Speerschneider, T, Lyngsø, C, Erikstrup, N, Burstein, E S, Weiner, D M, Walther, T, Makita, N, Iiri, T, Merten, N, Kostenis, E & Sheikh, S P 2008, ' Lack of evidence for AT1R/B2R heterodimerization in COS-7, HEK293, and NIH3T3 cells-How common is the AT1R/B2R heterodimer? ', Journal of Biological Chemistry, vol. 284, no. 3, pp. 1831-1839 . https://doi.org/10.1074/jbc.M804607200 |
| Popis: |
Udgivelsesdato: 2008-Nov-18 It has been suggested by AbdAlla and Quitterer, that the Angiotensin II type I receptor (AT1R) and the Bradykinin B2 Receptor (B2R) form constitutive heterodimers. Furthermore, they demonstrate that AT1R signalling significantly increases in the presence of the B2R. These findings suggest that heterodimerization and potentiation of AT1R signalling is a universal phenomenon that occurs as a natural consequence of simultaneous expression of the two receptors. Hence, this potential interaction is of great pharmacological and biological interest that adds an additional layer of complexity to the understanding of the crosstalk between the renin-angiotensin and kallikrein-kinin systems. Given the remarkable significance of this finding, scientists from four independent research groups have set out to reproduce and further examine the potential AT1R/B2R interaction. We have investigated functional potentiation by the B2R of AT1R signalling in three different cell lines, using multiple assays including Phosphoinositide (PI) hydrolysis, ERK activation, -arrestin recruitment, and Receptor Selection and Amplification Technology, and we have examined dimerization using Bioluminescence Resonance Energy Transfer and regulated secretion/aggregation technology. However, even though both the AT1Rs and B2Rs were functional in our systems, and the systems were fine tuned in order to detect small changes in receptor function, we failed to detect any functional modulation by or physical interaction between the two receptor proteins. In contrast to Abdallah et al., our data collectively suggest that AT1R/B2R heterodimerization does not occur as a natural consequence of their simultaneous expression in the same cell nor does the B2R influence the AT1R signalling. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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