AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration.
The vasopressor angiotensin II regulates vascular contractility and blood pressure through binding to type 1 angiotensin II receptors (AT1; refs 1, 2). Bradykinin, a vasodepressor, is a functional antagonist of angiotensin II (ref. 3). The two hormone systems are interconnected by the angiotensin-converting enzyme, which releases angiotensin II from its precursor and inactivates the vasodepressor bradykinin. Here we show that the AT1 receptor and the bradykinin (B2) receptor also communicate directly with each other. They form stable heterodimers, causing increased activation of G alpha(q) and G alpha(i) proteins, the two major signalling proteins triggered by AT1. Furthermore, the endocytotic pathway of both receptors changed with heterodimerization. This is the first example of signal enhancement triggered by heterodimerization of two different vasoactive hormone receptors.
AbdAlla
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Genetics Engineering and Biotechnology Research Institute, Manchiat El-Olama, El-Dekheela, Alexandria, Egypt.
Lother
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H
Quitterer
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U
D000804:Angiotensin II / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism; D002460:Cell Line; D019281:Dimerization; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000378:metabolism*; D015398:Signal Transduction
D007295:Inositol Phosphates; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D000804:Angiotensin II; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D001920:Bradykinin