Adenosine A1 receptor activation modulates human equilibrative nucleoside transporter 1 (hENT1) activity via PKC-mediated phosphorylation of serine-281

Cellular Signalling
Scott J HughesJames R Hammond

Abstract

Equilibrative nucleoside transporter subtype 1 (ENT1) is critical for the regulation of the biological activities of endogenous nucleosides such as adenosine, and for the cellular uptake of chemotherapeutic nucleoside analogs. Previous studies have implicated protein kinase C (PKC) in the regulation of ENT1 expression/function. It was hypothesized that hENT1 activity at the plasma membrane is regulated by PKC-mediated phosphorylation of Ser281. WT (wild-type)-hENT1 or S281A-hENT1 was stably transfected into a PK15 cell variant that is deficient in nucleoside transport. Using [(3)H]nitrobenzylthioinosine (NBMPR) binding and [(3)H]2-chloroadenosine uptake analyses, it was determined that S281A-hENT1 exhibited functional characteristics similar to WT-hENT1. Direct activation of PKC with PMA or indirect activation with the adenosine A1 receptor agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) led to significant increases in [(3)H]NBMPR binding and [(3)H]2-chloroadenosine uptake in WT-hENT1 transfected cells. The PKC inhibitor Gö6983 blocked these effects of both PMA and CCPA, and the CCPA-mediated increase was also blocked by the A1 adenosine receptor antagonist DPCPX. In contrast, neither PMA nor CCPA affected [(3)H]NBMPR binding...Continue Reading

References

Jul 6, 2006·Trends in Pharmacological Sciences·Anne E KingStephen A Baldwin
Mar 9, 2007·Cancer Metastasis Reviews·Jing ZhangCarol E Cass
Aug 1, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J D YoungS A Baldwin
Mar 16, 2011·Experimental Cell Research·Nicole M I NivillacImogen R Coe
Jan 23, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hung Wen LinMiguel A Perez-Pinzon

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Citations

May 26, 2016·Journal of Neurochemistry·Rafael BritoKarin C Calaza
Sep 16, 2016·Frontiers in Pharmacology·Priyank A ShenoyMaree T Smith
Dec 3, 2016·Nucleosides, Nucleotides & Nucleic Acids·Maliha ZafarImogen R Coe
Apr 5, 2017·International Journal of Molecular Sciences·Abdullah MayatiOlivier Fardel
Mar 25, 2016·American Journal of Physiology. Cell Physiology·Alex BicketImogen R Coe
Nov 25, 2020·Chemical Reviews·Nicholas J Wright, Seok-Yong Lee

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