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Heterodimerization of apelin receptor and neurotensin receptor 1 induces phosphorylation of ERK1/2and cell proliferationviaGαq-mediated mechanism
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Bai, Bo, Cai, Xin, Jiang, Yunlu, Karteris, Emmanouil and Chen, Jing (2014) Heterodimerization of apelin receptor and neurotensin receptor 1 induces phosphorylation of ERK1/2and cell proliferationviaGαq-mediated mechanism. Journal of Cellular and Molecular Medicine, Volume 18 (Number 10). pp. 2071-2081. doi:10.1111/jcmm.12404
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Official URL: http://dx.doi.org/10.1111/jcmm.12404
Abstract
Dimerization of G protein-coupled receptors (GPCRs) is crucial for receptor function including agonist affinity, efficacy, trafficking and specificity of signal transduction, including G protein coupling. Emerging data suggest that the cardiovascular system is the main target of apelin, which exerts an overall neuroprotective role, and is a positive regulator of angiotensin-converting enzyme 2 (ACE2) in heart failure. Moreover, ACE2 cleaves off C-terminal residues of vasoactive peptides including apelin-13, and neurotensin that activate the apelin receptor (APJ) and neurotensin receptor 1 (NTSR1) respectively, that belong to the A class of GPCRs. Therefore, based on the similar mode of modification by ACE2 at peptide level, the homology at amino acid level and the capability of forming dimers with other GPCRs, we have been suggested that APJ and NTSR1 can form a functional heterodimer. Using co-immunoprecipitation, BRET and FRET, we provided conclusive evidence of heterodimerization between APJ and NTSR1 in a constitutive and induced form. Upon agonist stimulation, hetrodimerization enhanced ERK1/2 activation and increased proliferation via activation of Gq α-subunits. These novel data provide evidence for a physiological role of APJ/NTSR1 heterodimers in terms of ERK1/2 activation and increased intracellular calcium and induced cell proliferation and provide potential new pharmaceutical targets for cardiovascular disease.
| Item Type: | Journal Article | ||||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Cell receptors, Neurotensin, Heart failure -- Physiology | ||||||||||
| Journal or Publication Title: | Journal of Cellular and Molecular Medicine | ||||||||||
| Publisher: | Wiley-Blackwell Publishing, Inc | ||||||||||
| ISSN: | 1582-1838 | ||||||||||
| Official Date: | October 2014 | ||||||||||
| Dates: |
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| Volume: | Volume 18 | ||||||||||
| Number: | Number 10 | ||||||||||
| Page Range: | pp. 2071-2081 | ||||||||||
| DOI: | 10.1111/jcmm.12404 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Open Access | ||||||||||
| Funder: | Guo jia zi ran ke xue ji jin wei yuan hui (China) [National Natural Science Foundation of China] (NSFC), Taishan Scholar Construction Special Fund | ||||||||||
| Grant number: | 30971081 (NNSFC), 31271243 (NNSFC), 81070961 (NNSFC) | ||||||||||
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