0 69

Differential regulation of cAMP-mediated gene transcription and ligand selectivity by MC3R and MC4R melanocortin receptors

Authors
 Eun Jin Lee  ;  Soo-Hyun Lee  ;  Jin-Won Jung  ;  Weontae Lee  ;  Byung Jin Kim  ;  Kye Won Park  ;  Sung-Kil Lim  ;  Chang-Ju Yoon  ;  Ja-Hyun Baik 
Citation
 European Journal of Biochemistry, Vol.268(3) : 582-591, 2001 
Journal Title
 European Journal of Biochemistry 
ISSN
 0014-2956 
Issue Date
2001
Abstract
Melanocortins are known to be involved in the regulation of feeding behavior. These hormones mediate their effects through G-protein-coupled receptors by stimulating adenylate cyclase. In this study we describe the functional response of melanocortin 4 receptor (MC4R) and melanocortin 3 receptor (MC3R) in HEK 293T cells, by using a luciferase reporter gene under the transcriptional control of a cAMP-responsive element (CRE) as a monitor of intracellular cAMP levels and cAMP-regulated gene expression. We were able to show that MC4R and MC3R expressed in the human cell line HEK 293T stimulate transcription induced by stimulation with different analogs of α-melanocyte-stimulating hormone (α-MSH) at different levels. In our assay of CRE-mediated gene transcription activity, α-MSH-ND was the most efficient α-MSH analog for MC4R whereas NDP-MSH was the most efficient for MC3R. Changing the His6 residue of α-MSH-ND to Gln or Lys markedly decreased CRE-mediated luciferase activity for MC3R compared with MC4R. On analysis by modeling the receptor–ligand complex by NMR, [Gln6]α-MSH-ND and [Lys6]α-MSH-ND showed different conformational interactions between MC3R and MC4R. Furthermore, the maximum coupling efficiency of MC4R and MC3R to G proteins was different; MC4R showed only 30–50% of the maximum activity induced by MC3R. In total, our results suggest that a differential receptor–ligand interaction is involved and that the relative interactions of MC3R and MC4R with G protein are possibly quantitatively and qualitatively different.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142567
Full Text
http://onlinelibrary.wiley.com/doi/10.1046/j.1432-1327.2001.01900.x/abstract
DOI
10.1046/j.1432-1327.2001.01900.x
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
임승길(Lim, Sung Kil)
Export
RIS (EndNote)
XLS (Excel)
XML
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse