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ERK5 Activation by Gq-Coupled Muscarinic Receptors Is Independent of Receptor Internalization and β-Arrestin Recruitment
被引:9
作者:

Sanchez-Fernandez, Guzman
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain
Univ Autonoma Madrid, UAM CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Inst Invest Sanitaria La Princesa, Madrid, Spain Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain

Cabezudo, Sofia
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h-index: 0
机构:
Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain
Univ Autonoma Madrid, UAM CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Inst Invest Sanitaria La Princesa, Madrid, Spain Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain

Garcia-Hoz, Carlota
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain
Univ Autonoma Madrid, UAM CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Inst Invest Sanitaria La Princesa, Madrid, Spain Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain

Tobin, Andrew B.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Leicester, Med Res Council Toxicol Unit, Leicester, Leics, England Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain

Mayor, Federico, Jr.
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h-index: 0
机构:
Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain
Univ Autonoma Madrid, UAM CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Inst Invest Sanitaria La Princesa, Madrid, Spain Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain

Ribas, Catalina
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain
Univ Autonoma Madrid, UAM CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
Inst Invest Sanitaria La Princesa, Madrid, Spain Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain
机构:
[1] Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Madrid, Spain
[2] Univ Autonoma Madrid, UAM CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
[3] Inst Invest Sanitaria La Princesa, Madrid, Spain
[4] Univ Leicester, Med Res Council Toxicol Unit, Leicester, Leics, England
来源:
PLOS ONE
|
2013年
/
8卷
/
12期
关键词:
GROWTH-FACTOR RECEPTOR;
PROTEIN;
TRAFFICKING;
ENDOCYTOSIS;
G-ALPHA(Q);
PATHWAY;
BETA-ARRESTIN-2;
CELLS;
GPCR;
D O I:
10.1371/journal.pone.0084174
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
G-protein-coupled receptors (GPCRs) are known to activate both G protein- and beta-arrestin-dependent signalling cascades. The initiation of mitogen-activated protein kinase (MAPK) pathways is a key downstream event in the control of cellular functions including proliferation, differentiation, migration and apoptosis. Both G proteins and beta-arrestins have been reported to mediate context-specific activation of ERK1/2, p38 and JNK MAPKs. Recently, the activation of ERK5 MAPK by Gq-coupled receptors has been described to involve a direct interaction between Gaq and two novel effectors, PKC zeta and MEK5. However, the possible contribution of beta-arrestin towards this pathway has not yet been addressed. In the present work we sought to investigate the role of receptor internalization processes and beta-arrestin recruitment in the activation of ERK5 by Gq-coupled GPCRs. Our results show that ERK5 activation is independent of M1 or M3 muscarinic receptor internalization. Furthermore, we demonstrate that phosphorylation-deficient muscarinic M1 and M3 receptors are still able to fully activate the ERK5 pathway, despite their reported inability to recruit beta-arrestins. Indeed, the overexpression of Gaq, but not that of beta-arrestin1 or beta-arrestin2, was found to potently enhance ERK5 activation by GPCRs, whereas silencing of beta-arrestin2 expression did not affect the activation of this pathway. Finally, we show that a beta-arrestin-biased mutant form of angiotensin II (SII; Sar1-Ile4-Ile8 AngII) failed to promote ERK5 phosphorylation in primary cardiac fibroblasts, as compared to the natural ligand. Overall, this study shows that the activation of ERK5 MAPK by model Gq-coupled GPCRs does not depend on receptor internalization, beta-arrestin recruitment or receptor phosphorylation but rather is dependent on Gaq-signalling.
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