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Roles for heterodimerization of APJ and B2R in promoting cell proliferation via ERK1/2-eNOS signaling pathway

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Ji, Bingyuan, Shang, Liyan, Wang, Chunmei, Wan, Lei, Cheng, Baohua and Chen, Jing (2020) Roles for heterodimerization of APJ and B2R in promoting cell proliferation via ERK1/2-eNOS signaling pathway. Cellular Signalling, 73 . 109671. doi:10.1016/j.cellsig.2020.109671 ISSN 0898-6568.

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Official URL: http://dx.doi.org/10.1016/j.cellsig.2020.109671

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Abstract

Apelin receptor (APJ) and bradykinin B2 receptor (B2R) play an important role in many physiological processes and share multiple similar characteristics in distribution and functions in the cardiovascular system. We first identified the endogenous expression of APJ and B2R in human umbilical vein endothelial cells (HUVECs) and their co-localization on human embryonic kidney (HEK) 293 cells membrane. A suite of bioluminescence and fluorescence resonance energy transfer (BRET and FRET), proximity ligation assay (PLA), and co-immunoprecipitation (Co-IP) was exploited to demonstrate formation of functional APJ and B2R heterodimer in HUVECs and transfected cells. Stimulation with apelin-13 and bradykinin (BK) increased the phosphorylation of the endothelial nitric oxide synthase (eNOS) in HUVECs, which could be inhibited by the silencing of APJ or B2R, indicating the APJ-B2R dimer is critical for eNOS phosphorylation in HUVECs. Furthermore, the increase of NOS and extracellular signal regulated kinases1/2 (ERK1/2) phosphorylation mediated by APJ/B2R dimer can be inhibited by U0126 and U73122, respectively, suggesting that the heterodimer might activate the PLC/ERK1/2/eNOS signaling pathway, and finally leading to a significant increase in cell proliferation. Thus, we uncovered for the first time the existence of APJ-B2R heterodimer and provided a promising new target in cardiovascular therapeutics.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Cell receptors, G proteins -- Receptors, Cell proliferation, Cell differentiation
Journal or Publication Title: Cellular Signalling
Publisher: Elsevier
ISSN: 0898-6568
Official Date: September 2020
Dates:
DateEvent
September 2020Published
12 May 2020Available
10 May 2020Accepted
Volume: 73
Article Number: 109671
DOI: 10.1016/j.cellsig.2020.109671
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Date of first compliant deposit: 20 May 2020
Date of first compliant Open Access: 12 May 2021
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
81671276[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
81870948 [NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
JYP2018KJ08Jining Medical Universityhttp://dx.doi.org/10.13039/501100008853
JYFC2018JS006Jining Medical Universityhttp://dx.doi.org/10.13039/501100008853

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