Linked Life Data

20332620

Source:http://linkedlifedata.com/resource/pubmed/id/20332620

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4-5
pubmed:dateCreated
2010-3-24
pubmed:abstractText
Several motifs found in the third intracellular loop of the M(3) muscarinic receptor are critical for G protein activation and scaffold protein interaction. However, how multiprotein complexes form is not fully understood. A minigene encoding the third intracellular loop of the M(3) muscarinic receptor was constructed to explore whether peptides from this intracellular region could act as inhibitors of the muscarinic multiprotein complex formation and signaling. We found that this construct, when co-expressed with the M(3) receptor, has the ability to act as a competitive antagonist of G protein receptors and receptor-scaffold/accessory proteins. Transient transfection of human embryonic kidney-293 cells with DNA encoding the human M(3) and M(5) receptor subtypes results in a carbachol-dependent increase of inositol phosphate. Co-expression of the M(3) third cytoplasmic loop minigene dramatically reduces both carbachol-mediated G protein activation and inositol phosphate accumulation. Minigene expression also abrogates activation of M(3) and M(5) receptor mitogen-activated protein kinases pathway. Furthermore, minigene expression led to reduced AKT activation. These data, together with results of co-immunoprecipitation of different scaffold and kinase proteins, provide experimental evidence for the role for the third cytoplasmic loop of the human M(3) muscarinic receptor in G-protein activation and multiprotein complex formation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1421-9778
pubmed:author
pubmed:copyrightInfo
2010 S. Karger AG, Basel.
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
397-408
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Impaired M(3) muscarinic acetylcholine receptor signal transduction through blockade of binding of multiple proteins to its third intracellular loop.
pubmed:affiliation
Neuroscience Department, Karolinska Institutet, Stockholm, Sweden. Dasiel.Borroto-Escuela@ki.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't