Interaction of the amyloid precursor like protein 1 with the alpha2A-adrenergic receptor increases agonist-mediated inhibition of adenylate cyclase

Cellular Signalling
Bernd WeberPeter H Tonner

Abstract

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 cotrans...Continue Reading

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Citations

Aug 10, 2006·Cell and Tissue Research·Lutz Hein
Aug 12, 2009·The Journal of Pharmacology and Experimental Therapeutics·Liyun WangStuart Maudsley
Apr 1, 2008·Expert Opinion on Drug Discovery·Annette Gilchrist
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Nov 29, 2016·Expert Review of Proteomics·Paulo BastosRui Vitorino
Dec 7, 2007·Journal of Proteome Research·Alexandre ZougmanMatthias Mann

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