FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2103144141> ?p ?o ?g. }

• W2103144141 endingPage "1314" @default.
• W2103144141 startingPage "1301" @default.
• W2103144141 abstract "Disruption of the hypothalamic melanocortin-4 receptor (MC4R) pathway results in obesity both in humans and rodents, demonstrating a crucial role for hypothalamic MC4Rs in the regulation of energy homeostasis. Because even haploinsufficiency of the MC4R gene can cause obesity in humans and mice, subtle changes in receptor numbers or signaling are likely to impact upon the regulation of food intake and energy expenditure. Little is known about the intracellular regulation of MC4R signaling. Using GT1-7 cells, we show for the first time that the MC4R undergoes ligand-mediated desensitization. We then addressed the possible mechanisms underlying the desensitization using HEK293 and COS-1 cells transfected with hemagglutinin-tagged human MC4R. Preexposure of GT1-7 cells that express endogenous MC4R to the agonist for MC4R, alpha-melanocyte-stimulating hormone, resulted in impaired cAMP formation to a second challenge of alpha-melanocyte-stimulating hormone. The desensitization of MC4R was accompanied by time-dependent internalization of the receptor in HEK293 cells, which was partly inhibited by pretreatment with a specific protein kinase A (PKA) inhibitor, H89. In COS-1 cells, overexpression of dominant-negative G protein-coupled receptor kinase (GRK) 2-K220R partly inhibited the agonist-mediated internalization of MC4R, whereas it did not in HEK293 cells. Overexpression of dominant-negative mutants of beta-arrestin1-V53D and dynamin I-K44A prevented agonist-mediated internalization of MC4R. Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor. Our data demonstrate that, through PKA-, GRK-, beta-arrestin-, and dynamin-dependent processes, MC4R undergoes internalization in response to agonist, thereby providing novel insights into the regulation of MC4R signaling." @default.
• W2103144141 created "2016-06-24" @default.
• W2103144141 creator A5017534508 @default.
• W2103144141 creator A5043952560 @default.
• W2103144141 creator A5049112095 @default.
• W2103144141 creator A5057920752 @default.
• W2103144141 date "2003-04-01" @default.
• W2103144141 modified "2023-09-25" @default.
• W2103144141 title "Regulation of Melanocortin-4 Receptor Signaling: Agonist-Mediated Desensitization and Internalization" @default.
• W2103144141 cites W1033010459 @default.
• W2103144141 cites W1489925379 @default.
• W2103144141 cites W1498791370 @default.
• W2103144141 cites W1504756577 @default.
• W2103144141 cites W1512875938 @default.
• W2103144141 cites W1539401343 @default.
• W2103144141 cites W1544954412 @default.
• W2103144141 cites W1554843415 @default.
• W2103144141 cites W1561443084 @default.
• W2103144141 cites W1593834989 @default.
• W2103144141 cites W1603105681 @default.
• W2103144141 cites W1604209299 @default.
• W2103144141 cites W1639930240 @default.
• W2103144141 cites W1832014310 @default.
• W2103144141 cites W1909076506 @default.
• W2103144141 cites W1915373236 @default.
• W2103144141 cites W1965574341 @default.
• W2103144141 cites W1967965496 @default.
• W2103144141 cites W1972000079 @default.
• W2103144141 cites W1975386197 @default.
• W2103144141 cites W1982201097 @default.
• W2103144141 cites W1989899477 @default.
• W2103144141 cites W1992620183 @default.
• W2103144141 cites W1994493683 @default.
• W2103144141 cites W1994957236 @default.
• W2103144141 cites W1996713062 @default.
• W2103144141 cites W2002768212 @default.
• W2103144141 cites W2004151175 @default.
• W2103144141 cites W2006824774 @default.
• W2103144141 cites W2010142606 @default.
• W2103144141 cites W2012496594 @default.
• W2103144141 cites W2016730049 @default.
• W2103144141 cites W2023629636 @default.
• W2103144141 cites W2023661096 @default.
• W2103144141 cites W2033001374 @default.
• W2103144141 cites W2034172498 @default.
• W2103144141 cites W2036329205 @default.
• W2103144141 cites W2037204799 @default.
• W2103144141 cites W2041282147 @default.
• W2103144141 cites W2041654178 @default.
• W2103144141 cites W2049796382 @default.
• W2103144141 cites W2051192888 @default.
• W2103144141 cites W2055079075 @default.
• W2103144141 cites W2057089327 @default.
• W2103144141 cites W2059247616 @default.
• W2103144141 cites W2060207881 @default.
• W2103144141 cites W2061248581 @default.
• W2103144141 cites W2062426253 @default.
• W2103144141 cites W2063807916 @default.
• W2103144141 cites W2065389660 @default.
• W2103144141 cites W2067698573 @default.
• W2103144141 cites W2072419382 @default.
• W2103144141 cites W2076983520 @default.
• W2103144141 cites W2080815758 @default.
• W2103144141 cites W2087163465 @default.
• W2103144141 cites W2090020265 @default.
• W2103144141 cites W2092807846 @default.
• W2103144141 cites W2094469376 @default.
• W2103144141 cites W2097446876 @default.
• W2103144141 cites W2118192748 @default.
• W2103144141 cites W2125468282 @default.
• W2103144141 cites W2133635537 @default.
• W2103144141 cites W2147741187 @default.
• W2103144141 cites W2147888023 @default.
• W2103144141 cites W2148391313 @default.
• W2103144141 cites W2149239576 @default.
• W2103144141 cites W2151775257 @default.
• W2103144141 cites W2153370001 @default.
• W2103144141 cites W2167840664 @default.
• W2103144141 cites W4212849655 @default.
• W2103144141 cites W66891075 @default.
• W2103144141 doi "https://doi.org/10.1210/en.2002-220931" @default.
• W2103144141 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12639913" @default.
• W2103144141 hasPublicationYear "2003" @default.
• W2103144141 type Work @default.
• W2103144141 sameAs 2103144141 @default.
• W2103144141 citedByCount "121" @default.
• W2103144141 countsByYear W21031441412012 @default.
• W2103144141 countsByYear W21031441412013 @default.
• W2103144141 countsByYear W21031441412014 @default.
• W2103144141 countsByYear W21031441412015 @default.
• W2103144141 countsByYear W21031441412016 @default.
• W2103144141 countsByYear W21031441412017 @default.
• W2103144141 countsByYear W21031441412018 @default.
• W2103144141 countsByYear W21031441412019 @default.
• W2103144141 countsByYear W21031441412020 @default.
• W2103144141 countsByYear W21031441412021 @default.
• W2103144141 countsByYear W21031441412022 @default.
• W2103144141 crossrefType "journal-article" @default.

• next