Abstract
G-protein-coupled receptors (GPCRs) are known to activate both G protein- and β-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 β-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 Gαq and two novel effectors, PKCζ and MEK5. However, the possible contribution of β-arrestin towards this pathway has not yet been addressed. In the present work we sought to investigate the role of receptor internalization processes and β-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 β-arrestins. Indeed, the overexpression of Gαq, but not that of β-arrestin1 or β-arrestin2, wa...Continue Reading
References
Jul 19, 1996·The Journal of Biological Chemistry·L M Tolbert, J Lameh
Apr 27, 2000·The Journal of Biological Chemistry·S FukuharaJ S Gutkind
Nov 25, 2000·Science·P H McDonaldR J Lefkowitz
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·L M LuttrellR J Lefkowitz
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·Kristen L PierceRobert J Lefkowitz
Dec 10, 2002·The Journal of Biological Chemistry·Thangiah Geetha, Marie W Wooten
May 15, 2003·Endocrinology·Zsuzsanna GáborikLászló Hunyady
Sep 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Huijun WeiRobert J Lefkowitz
May 1, 2004·The Journal of Biological Chemistry·Juliana S Popova, Mark M Rasenick
Jun 19, 2004·The Journal of Biological Chemistry·Seungkirl AhnRobert J Lefkowitz
Dec 14, 2006·Current Oncology Reports·Halle C F Moore
Feb 20, 2007·Annual Review of Physiology·Scott M DeWireSudha K Shenoy
Feb 23, 2007·Molecular Biology of the Cell·Miriam ShmuelYoram Altschuler
Apr 4, 2007·The Journal of Cell Biology·Ignacio TorrecillaAndrew B Tobin
Nov 13, 2008·The Journal of Biological Chemistry·Xiufeng SongVsevolod V Gurevich
Mar 4, 2009·The Journal of Biological Chemistry·Jihee KimRobert J Lefkowitz
Aug 22, 2009·Nature Reviews. Molecular Cell Biology·Alexander Sorkin, Mark von Zastrow
Mar 5, 2010·The Journal of Biological Chemistry·Carlota García-HozCatalina Ribas
Aug 31, 2010·The Journal of Pharmacology and Experimental Therapeutics·Jonathan D ViolinMichael W Lark
Nov 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kok Choi KongAndrew B Tobin
May 25, 2011·Methods in Molecular Biology·Richard J WardGraeme Milligan
Jan 11, 2012·The Journal of Biological Chemistry·Carlota García-HozCatalina Ribas
Citations
Apr 1, 2015·Future Medicinal Chemistry·Zutao YuQianbin Li
Sep 4, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cédric BruléLaurent Prézeau
Feb 19, 2016·The Journal of Biological Chemistry·Guzmán Sánchez-FernándezCatalina Ribas
Dec 14, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniela Volpato, Ulrike Holzgrabe