Synergistic activation of thrombin and angiotensin II receptors revealed by bioluminescence resonance energy transfer.
Isra Al ZamelAbdulrasheed PalakkottMohammad Akli AyoubPublished in: FEBS letters (2021)
We recently reported a physical interaction between the angiotensin II (AngII) receptor (AT1R) and thrombin receptor (PAR1) in HEK293 cells using bioluminescence resonance energy transfer (BRET) technology. This was characterized by thrombin trans-activating AT1R and the synergistic responses of the AT1R-PAR1 complex. Here, we investigated the other face of the coin by examining the effect of AT1R on PAR1 activity using BRET. AngII/AT1R did not promote PAR1 activation in the absence of thrombin. However, the combination of thrombin and AngII resulted in their synergistic/allosteric action. Moreover, AngII/AT1R potentiated the maximal thrombin responses, suggesting specific conformational changes within the AT1R-PAR1 complex. Overall, our data confirm the functional AT1R-PAR1 interplay and further support the implication of both AT1R and PAR1 protomers in their synergistic interaction as previously reported.
Keyphrases
- energy transfer
- angiotensin ii
- quantum dots
- angiotensin converting enzyme
- vascular smooth muscle cells
- induced apoptosis
- mental health
- cell proliferation
- heart rate
- electronic health record
- body composition
- molecular dynamics simulations
- oxidative stress
- binding protein
- deep learning
- mass spectrometry
- artificial intelligence