Linked Life Data

18341518

Source:http://linkedlifedata.com/resource/pubmed/id/18341518

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-9-19
pubmed:abstractText
Melatonin, a molecule implicated in a variety of diseases, including cancer, often exerts its effects through G-protein-coupled melatonin receptors, MT(1) and MT(2). In this study, we sought to understand further the domains involved in the function and desensitization patterns of these receptors through site-directed mutagenesis. Two mutations were constructed in the cytoplasmic C-terminal tail of each receptor subtype: (i) a cysteine residue in the C-terminal tail was mutated to alanine, thus removing a putative palmitoylation site, and a site possibly required for normal receptor function (MT(1)C7.72A and MT(2)C7.77A) and (ii) the C-terminal tail in the MT(1) and MT(2) receptors was truncated, removing the putative phosphorylation and beta-arrestin binding sites (MT(1)Y7.64 and MT(2)Y7.64). These mutations did not alter the affinity of 2-[(125)I]-iodomelatonin binding to the MT(1) or MT(2) receptors. Using confocal microscopy, it was determined that the putative palmitoylation site (cysteine residue) did not play a role in receptor internalization; however, this residue was essential for receptor function, as determined by 3',5'-cyclic adenosine monophosphate (cAMP) accumulation assays. Truncation of the C-terminal tail of both receptors (MT(1)Y7.64 and MT(2)Y7.64) inhibited internalization as well as the cAMP response, suggesting the importance of the C-terminal tail in these receptor functions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1600-079X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
212-8
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
C-terminal domains within human MT1 and MT2 melatonin receptors are involved in internalization processes.
pubmed:affiliation
Division of Pharmaceutical Sciences, School of Pharmacy, Bayer School of Natural and Environmental Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't