Linked Life Data

20214954

Source:http://linkedlifedata.com/resource/pubmed/id/20214954

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2010-4-26
pubmed:abstractText
The melanocortin-4 receptor (MC4R) is involved in regulating energy homeostasis; mutations in this gene have been associated with 1-5% of early-onset human obesity. The aim of this study was to functionally characterize MC4R mutations identified in morbidly obese subjects living in Southern Italy. We studied their ligand binding, signaling pathway and subcellular localization. As expected, mutants Q43X and S19fsX51, which produce truncated forms of receptor, were devoid of activity. The activity of mutants W174C and A175T were very different even though the mutations are adjacent and are in the same transmembrane helix (TMH). In fact, the production and expression of mutant A175T on the plasma-membrane (PM) was similar to that of the wild-type (wt) receptor and the mutant retained 70% of wt receptor activity; on the contrary, the production of W174C mutant in the cytoplasm was similar to that of the wt receptor and mutant A175T but was only barely detectable on the PM and was devoid of activity. Confocal microscopy showed that W174C remained entrapped in the endoplasmic reticulum (ER) of the cells. Structural analysis showed that substitution of Trp174, located in the middle of TMH4 and 100% conserved in all known MC4Rs, with Cys could impair the relative orientation of TMH2 and TMH4 thereby affecting the overall protein architecture. Furthermore, co-expression studies showed that mutant A175T but not W174C had a dominant negative effect on the wt receptor activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1879-0038
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
457
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-41
pubmed:meshHeading
pubmed-meshheading:20214954-Amino Acid Substitution, pubmed-meshheading:20214954-Cells, Cultured, pubmed-meshheading:20214954-Humans, pubmed-meshheading:20214954-Italy, pubmed-meshheading:20214954-Ligands, pubmed-meshheading:20214954-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:20214954-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:20214954-Models, Molecular, pubmed-meshheading:20214954-Mutant Proteins, pubmed-meshheading:20214954-Obesity, Morbid, pubmed-meshheading:20214954-Phosphorylation, pubmed-meshheading:20214954-Protein Binding, pubmed-meshheading:20214954-Receptor, Melanocortin, Type 4, pubmed-meshheading:20214954-Signal Transduction, pubmed-meshheading:20214954-Structure-Activity Relationship, pubmed-meshheading:20214954-Tissue Distribution, pubmed-meshheading:20214954-Transfection, pubmed-meshheading:20214954-alpha-MSH
pubmed:year
2010
pubmed:articleTitle
Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy.
pubmed:affiliation
Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Facoltà di Scienze Motorie, Università Parthenope, Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't