کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815122 | 1058449 | 2015 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Adenosine A1 receptor activation modulates human equilibrative nucleoside transporter 1 (hENT1) activity via PKC-mediated phosphorylation of serine-281
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کلمات کلیدی
NMGGö6983ENT1NBMPRCCPAPKCDPCPX8-Cyclopentyl-1,3-dipropylxanthine - 8-Cyclopentyl-1،3-dipropylxanthineN-Methylglucamine - N-متیل گلوکامینTransport - حمل و نقل یا ترابریMembranes - غشاءMEM - مامانRegulation - مقرراتMutagenesis - موتاژنزwild-type - نوع وحشیnitrobenzylmercaptopurine riboside - نیتروبنزیل مروپاپورپورین ریبوزیدNucleoside - هسته ایProtein kinase C - پروتئین کیناز سیKinase - کیناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
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 [3H]nitrobenzylthioinosine (NBMPR) binding and [3H]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 [3H]NBMPR binding and [3H]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 [3H]NBMPR binding or [3H]2-chloroadenosine uptake in cells transfected with S281A-hENT1. shRNAi silencing studies implicated PKCδ in this regulation of hENT1 activity. Immunocytochemical analysis and cell surface biotinylation assays showed that activation of PKC with PMA, but not CCPA, led to a significant increase in the plasma membrane localization of hENT1. These data suggest that phosphorylation of hENT1 by PKC has effects on both the function and subcellular trafficking of hENT1. This signaling pathway represents a feedback loop whereby adenosine receptor signaling can lead to increased adenosine reuptake into cells via hENT1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 5, May 2015, Pages 1008-1018
Journal: Cellular Signalling - Volume 27, Issue 5, May 2015, Pages 1008-1018
نویسندگان
Scott J. Hughes, Xenia Cravetchi, Gonzalo Vilas, James R. Hammond,