beta-Arrestin1 interacts with the G-protein subunits beta1gamma2 and promotes beta1gamma2-dependent Akt signalling for NF-kappaB activation.

The Biochemical Journal
Ming YangRichard D Ye

Abstract

beta-Arrestins are known to regulate G-protein signalling through interactions with their downstream effectors. In the present study, we report that beta-arrestin1 associates with the G-protein beta1gamma2 subunits in transfected cells, and purified beta-arrestin1 interacts with G(beta1gamma2) derived from in vitro translation. Deletion mutagenesis of beta-arrestin1 led to the identification of a region, comprising amino acids 181-280, as being responsible for its interaction with G(beta1gamma2). Overexpression of beta-arrestin1 facilitates G(beta1gamma2)-mediated Akt phosphorylation, and inhibition of endogenous beta-arrestin1 expression by siRNA (small interfering RNA) diminishes this effect. Through investigation of NF-kappaB (nuclear factor kappaB), a transcription factor regulated by Akt signalling, we have found that overexpression of beta-arrestin1 significantly enhances G(beta1gamma2)-mediated nuclear translocation of NF-kappaB proteins and expression of a NF-kappaB-directed luciferase reporter. Overexpression of beta-arrestin1 also promotes bradykinin-induced, G(betagamma)-mediated NF-kappaB luciferase-reporter expression, which is reverted by silencing the endogenous beta-arrestin1 with a specific siRNA. These results...Continue Reading

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Citations

Mar 1, 2012·Acta Pharmacologica Sinica·Lei Sun, Richard D Ye
Jan 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Vanessa L WehbiJean-Pierre Vilardaga
Nov 26, 2010·The Journal of Biological Chemistry·Dongjun LiDonna S Woulfe
Jan 24, 2012·The Journal of Biological Chemistry·Crystal Zoe HoeppnerRichard D Ye
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Aug 8, 2015·American Journal of Respiratory and Critical Care Medicine·Raymond L BenzaHemant K Tiwari
Apr 6, 2013·Trends in Pharmacological Sciences·Alan V Smrcka
Jun 20, 2012·Trends in Pharmacological Sciences·Jean-Pierre VilardagaTimothy N Feinstein
Dec 14, 2016·Biomolecules & Therapeutics·Chengchun MinKyeong-Man Kim
Mar 31, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jianyu YuJiajun Du
Nov 1, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aurélie TréfierPascale Crépieux
Sep 16, 2017·International Journal of Endocrinology·I S StafeevYe V Parfyonova
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Nov 28, 2019·Experimental and Therapeutic Medicine·Zhe ChenLei Xiang
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Mar 25, 2021·Archives of Pharmacal Research·Ningning Sun, Kyeong-Man Kim

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