Linked Life Data

16531006

Source:http://linkedlifedata.com/resource/pubmed/id/16531006

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-8-21
pubmed:abstractText
Alpha2-adrenergic receptor agonists exert potent analgesic and sedative/hypnotic effects. In addition, they have been shown to be neuroprotective, but the mechanisms of these actions are still poorly defined. To isolate proteins that may control alpha2-adrenergic receptor function or trafficking, we performed a two-hybrid screen using the carboxy-terminal fourth intracellular tail of the alpha2A-adrenergic receptor as bait. This screen identified the amyloid precursor like protein 1 (APLP1), a homologue of the beta-amyloid precursor protein involved in Alzheimer's disease, as alpha2A-adrenergic receptor-binding protein. GST affinity chromatography revealed that APLP1 specifically interacts with all three human alpha2-adrenergic receptor subtypes and deletion mutant analysis confined the APLP1 domain involved in binding to alpha2-adrenergic receptors to the 13 amino acid residues Ser599-Ala611. Coimmunoprecipitations of transiently transfected cells with epitope-tagged APLP1 and alpha2-adrenergic receptors confirmed the interaction. Agonist treatment tended to increase the amount of alpha2A-adrenergic receptor associated with APLP1 while coimmunoprecipitations were not affected by the state of receptor phosphorylation or cotransfection of arrestin-3. Confocal laser microscopy showed that APLP1 causes a considerable shift of the alpha2A-adrenergic receptor localization from plasma membrane to intracellular compartments. Furthermore, cotransfection of alpha2A-adrenergic receptor and APLP1 into HEK293 cells significantly increased norepinephrine mediated inhibition of adenylate cyclase activity. These results suggest a possible role of APLP1 in regulation of alpha2A-adrenergic receptor trafficking. Moreover, we speculate that this interaction may present one mechanism by which alpha2-adrenergic receptor agonists exert their neuroprotective effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0898-6568
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1748-57
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16531006-Adenylate Cyclase, pubmed-meshheading:16531006-Amino Acid Sequence, pubmed-meshheading:16531006-Amyloid beta-Protein Precursor, pubmed-meshheading:16531006-Animals, pubmed-meshheading:16531006-Arrestins, pubmed-meshheading:16531006-COS Cells, pubmed-meshheading:16531006-Cercopithecus aethiops, pubmed-meshheading:16531006-Glutathione Transferase, pubmed-meshheading:16531006-HeLa Cells, pubmed-meshheading:16531006-Humans, pubmed-meshheading:16531006-Molecular Sequence Data, pubmed-meshheading:16531006-Phosphorylation, pubmed-meshheading:16531006-Protein Binding, pubmed-meshheading:16531006-Protein Structure, Tertiary, pubmed-meshheading:16531006-Protein Transport, pubmed-meshheading:16531006-Receptors, Adrenergic, alpha-2, pubmed-meshheading:16531006-Two-Hybrid System Techniques
pubmed:year
2006
pubmed:articleTitle
Interaction of the amyloid precursor like protein 1 with the alpha2A-adrenergic receptor increases agonist-mediated inhibition of adenylate cyclase.
pubmed:affiliation
Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 21, 24105 Kiel, Germany. weber@anaesthesie.uni-kiel.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't