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Identification of transmembrane domains that regulate spatial arrangements and activity of prokineticin receptor 2 dimers

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Title: Identification of transmembrane domains that regulate spatial arrangements and activity of prokineticin receptor 2 dimers
Author(s): Sposini, S
Caltabiano, G
Hanyaloglu, AC
Miele, R
Item Type: Journal Article
Abstract: The chemokine prokineticin 2 (PK2) activates its cognate G protein-coupled receptor (GPCR) PKR2 to elicit various downstream signaling pathways involved in diverse biological processes. Many GPCRs undergo dimerization that can modulate a number of functions including membrane delivery and signal transduction. The aim of this study was to elucidate the interface of PKR2 protomers within dimers by analyzing the ability of PKR2 transmembrane (TM) deletion mutants to associate with wild type (WT) PKR2 in yeast using co-immunoprecipitation and mammalian cells using bioluminescence resonance energy transfer. Deletion of TMs 5-7 resulted in a lack of detectable association with WT PKR2, but could associate with a truncated mutant lacking TMs 6-7 (TM1-5). Interestingly, TM1-5 modulated the distance, or organization, between protomers and positively regulated Gαs signaling and surface expression of WT PKR2. We propose that PKR2 protomers form type II dimers involving TMs 4 and 5, with a role for TM5 in modulation of PKR2 function.
Publication Date: 6-Nov-2014
Date of Acceptance: 30-Oct-2014
URI: http://hdl.handle.net/10044/1/31246
DOI: http://dx.doi.org/10.1016/j.mce.2014.10.024
ISSN: 1872-8057
Publisher: Elsevier
Start Page: 362
End Page: 372
Journal / Book Title: Molecular and Cellular Endocrinology
Volume: 399
Copyright Statement: © 2014 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Bioluminescence resonance energy transfer (BRET)
Dimerization
G-protein coupled receptor (GPCR)
Molecular modeling
Prokineticin receptor 2 (PKR2)
Signaling
Amino Acid Sequence
Animals
CHO Cells
Cricetinae
Cricetulus
HEK293 Cells
Humans
Protein Multimerization
Protein Structure, Tertiary
Receptors, G-Protein-Coupled
Receptors, Peptide
Sequence Deletion
CHO Cells
Animals
Humans
Cricetulus
Receptors, G-Protein-Coupled
Receptors, Peptide
Sequence Deletion
Amino Acid Sequence
Protein Structure, Tertiary
Cricetinae
Protein Multimerization
HEK293 Cells
Endocrinology & Metabolism
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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