LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Bai, Bo; Cai, Xin; Jiang, Yunlu; Karteris, Emmanouil; Chen, Jing (2014)
Publisher: Wiley-Blackwell Publishing, Inc
Languages: English
Types: Article
Subjects: QP

Classified by OpenAIRE into

mesheuropmc: hormones, hormone substitutes, and hormone antagonists
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.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • Sato T, Suzuki T, Watanabe H, et al. Apelin is a positive regulator of ACE2 in failing hearts. J Clin Invest. 2013; 123: 5203-11.
    • Meng Y, Yu CH, Li W, et al. Angiotensinconverting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-kappaB pathway. Am J Respir Cell Mol Biol. 2014; 50: 723-36.
    • Danilczyk U, Penninger JM. Angiotensinconverting enzyme II in the heart and the kidney. Circ Res. 2006; 98: 463-71.
    • Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002; 277: 14838-43.
    • Trends Pharmacol Sci. 2014; 35: 247-55.
    • The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis. J Endocrinol. 2013; 219: R13-35.
    • Li Y, Chen J, Bai B, et al. Heterodimerization of human apelin and kappa opioid receptors: roles in signal transduction. Cell Signal. 2012; 24: 991-1001.
    • Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000; 87: E1-9.
    • Koschatzky S, Gmeiner P. Selective agonists for dopamine/neurotensin receptor heterodimers. ChemMedChem. 2012; 7: 509-14.
    • Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, 12.
    • Biophys J . 2009; 96: 964-73.
    • Bai B, Liu L, Zhang N, et al. Heterodimerization of human apelin and bradykinin 1 receptors: novel signal transduction characteristics. Cell Signal. 2014; 26: 1549-59.
    • Pfleger KD, Seeber RM, Eidne KA. Bioluminescence resonance energy transfer (BRET) for the real-time detection of protein-protein interactions. Nat Protoc. 2006; 1: 337-45.
    • Lohse MJ, Nuber S, Hoffmann C. Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling. Pharmacol Rev. 2012; 64: 299-336.
    • Dimerization of the class A G protein-coupled neurotensin receptor NTS1 alters G protein interaction. Proc Natl Acad Sci USA.
    • Li L, Li L, Xie F, et al. Jagged-1/Notch3 signaling transduction pathway is involved in apelin-13-induced vascular smooth muscle cells proliferation. Acta Biochim Biophys Sin. 2013; 45: 875-81.
    • [Apelin signalisation and vascular physiopathology]. J Soc Biol. 2009; 203: 171-9.
    • Wang G, Kundu R, Han S, et al. Ontogeny of apelin and its receptor in the rodent gastrointestinal tract. Regul Pept. 2009; 158: 32-9.
    • Hwang JI, Kim DK, Kwon HB, et al. Phylogenetic history, pharmacological features, and signal transduction of neurotensin 27.
    • Apelin enhances cardiac neovascularization after myocardial infarction by recruiting aplnr+ circulating cells. Circ Res. 2012; 111: 585-98.
    • Bai B, Tang J, Liu H, et al. Apelin-13 induces ERK1/2 but not p38 MAPK activation through coupling of the human apelin receptor to the Gi2 pathway. Acta Biochim Biophys Sin. 2008; 40: 311-8.
    • Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk? Mol Pharmacol. 2005; 67: 1697-704.
    • Kang Y, Kim J, Anderson JP, et al. ApelinAPJ signaling is a critical regulator of endothelial MEF2 activation in cardiovascular development. Circ Res. 2013; 113: 22-31.
    • Pharmacol Rev. 2010; 62: 701-25.
    • Rios C, Gomes I, Devi LA. mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis. Br J Pharmacol. 2006; 148: 387-95.
    • Fuentes A, Goldkrand JW. Angiotensin-converting enzyme activity in hypertensive subjects after magnesium sulfate therapy. Am J Obstet Gynecol. 1987; 156: 1375-9.
  • No related research data.
  • Discovered through pilot similarity algorithms. Send us your feedback.

Share - Bookmark

Cite this article