Carboxy-Terminal Phosphoregulation of the Long Splice Isoform of Free-Fatty Acid Receptor-4 Mediates β-Arrestin Recruitment and Signaling to ERK1/2.

Molecular Pharmacology
Ilya S SenatorovNader H Moniri

Abstract

Free-fatty acid receptor-4 (FFA4), previously termed GPR120, is a G protein-coupled receptor (GPCR) for medium and long-chained fatty acids, agonism of which can regulate a myriad of metabolic, sensory, inflammatory, and proliferatory signals. Two alternative splice isoforms of FFA4 exist that differ by the presence of an additional 16 amino acids in the longer (FFA4-L) transcript, which has been suggested to be an intrinsically β-arrestin-biased GPCR. Although the shorter isoform (FFA4-S) has been studied more extensively, very little is known about mechanisms of regulation or signaling of the longer isoform. Because β-arrestin recruitment is dependent on receptor phosphorylation, in the current study, we used the endogenous agonist docosahexaenoic acid (DHA) to examine the mechanisms of FFA4-L phosphorylation, as well as DHA-dependent β-arrestin recruitment and DHA-dependent extracellular-signal regulated kinase-1/2 (ERK1/2) signaling in human embryonic kidney 293 cells. Our results reveal differences in basal phosphorylation of the two FFA4 isoforms, and we show that DHA-mediated phosphorylation of FFA4-L is primarily regulated by G protein-coupled receptor kinase 6, whereas protein kinase-C can also contribute to agonist-in...Continue Reading

References

Nov 1, 1996·Trends in Pharmacological Sciences·T T ChuangA De Blasi
Oct 6, 1998·Annual Review of Biochemistry·J A PitcherR J Lefkowitz
Jun 7, 2000·Pigment Cell Research·R Buscà, R Ballotti
Sep 23, 2003·Cellular Signalling·Petronila PenelaFederico Mayor
Dec 5, 2003·Trends in Pharmacological Sciences·Jonathon M WilletsStefan R Nahorski
Dec 28, 2004·Nature Medicine·Akira HirasawaGozoh Tsujimoto
Jan 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xiu-Rong RenRobert J Lefkowitz
Sep 3, 2009·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Kristina MooreRuth Duffy
Aug 27, 2011·Chemical Senses·Maria Mercedes GalindoMaik Behrens
Jan 28, 2012·Molecular Pharmacology·Sarah-Jane WatsonNicholas D Holliday
May 12, 2015·The Journal of Veterinary Medical Science·Masahiro MiyabeKatsumi Ishioka
Jun 16, 2015·BioMed Research International·Tongxing SongJian Peng
Jul 18, 2015·Annual Review of Nutrition·Trond Ulven, Elisabeth Christiansen
Nov 29, 2015·Molecular Systems Biology·Hyunryul RyuOlivier Pertz
Mar 24, 2016·Biochemical Pharmacology·Elisa Alvarez-Curto, Graeme Milligan
Apr 8, 2017·Molecular Pharmacology·Kenneth R WattersonGraeme Milligan
Jul 25, 2017·Trends in Pharmacological Sciences·Graeme MilliganAndrew B Tobin
Jan 25, 2018·Nature Communications·Manuel GrundmannEvi Kostenis
Mar 1, 2018·The Journal of Biological Chemistry·Thomas F PackMarc G Caron
Jan 1, 2019·World Journal of Biological Chemistry·Vsevolod V Gurevich, Eugenia V Gurevich

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Citations

Feb 26, 2021·Biochemical Pharmacology·Nader H Moniri, Qadan Farah

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