Linked Life Data

15358050

Source:http://linkedlifedata.com/resource/pubmed/id/15358050

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-9-10
pubmed:abstractText
Leptin is a cytokine secreted by the adipose tissue that is involved in the control of body weight. We previously showed that a point mutation (R105W) in leptin results in leptin deficiency, marked obesity and hypogonadism in humans adults. Expression in COS1 cells showed impaired secretion and intracellular accumulation of the mutated protein. However, impaired secretion of the mutant leptin had not been demonstrated in adipose cells. In this work, we demonstrate that secretion of R105W mutant is impaired in rat and human adipocytes. We also show that R105W mutant expressed in COS1 cells and in PAZ6 adipocytes forms large molecular aggregates that cannot cross a filtration membrane with a cut-off of 100 kDa. Moreover, we have engineered, by site directed mutagenesis, the cDNAs coding for leptin in which either Cys 117, Cys 167, or both, were replaced by a serine. When expressed in COS1 cells or PAZ6 adipocytes, cysteine mutants also show impaired secretion and formation of large molecular aggregates. Therefore, our work indicates that the formation of an intramolecular disulfide bridge is necessary for normal processing and secretion of leptin. Moreover, the similarity of the behavior of R105W mutant and cystein mutants suggests that the lack of secretion observed with the naturally occurring mutant could result from impaired disulfide bond formation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0300-9084
pubmed:author
pubmed:issnType
Print
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
351-6
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The formation of an intrachain disulfide bond in the leptin protein is necessary for efficient leptin secretion.
pubmed:affiliation
Department of Cell Biology, Institut Cochin, UMR CNRS 8104, Inserm U567, Université Paris 5, 22, rue Méchain, 75014 Paris, France.
pubmed:publicationType
Journal Article