Article (Scientific journals)
New paradigms in chemokine receptor signal transduction: Moving beyond the two-site model.
Kleist, Andrew B.; Getschman, Anthony E.; Ziarek, Joshua J. et al.
2016In Biochemical Pharmacology
Peer Reviewed verified by ORBi
 

Files


Full Text
New Paradigms in chemokine receptor signal transduction, moving beyond the two-site model (Kleist A. et al., 2016).pdf
Publisher postprint (1.74 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
7TMR activation; Biased agonism; Chemokine stoichiometry; Seven transmembrane-spanning receptor (7TMR); Two-site model
Abstract :
[en] Chemokine receptor (CKR) signaling forms the basis of essential immune cellular functions, and dysregulated CKR signaling underpins numerous disease processes of the immune system and beyond. CKRs, which belong to the seven transmembrane domain receptor (7TMR) superfamily, initiate signaling upon binding of endogenous, secreted chemokine ligands. Chemokine-CKR interactions are traditionally described by a two-step/two-site mechanism, in which the CKR N-terminus recognizes the chemokine globular core (i.e. site 1 interaction), followed by activation when the unstructured chemokine N-terminus is inserted into the receptor TM bundle (i.e. site 2 interaction). Several recent studies challenge the structural independence of sites 1 and 2 by demonstrating physical and allosteric links between these supposedly separate sites. Others contest the functional independence of these sites, identifying nuanced roles for site 1 and other interactions in CKR activation. These developments emerge within a rapidly changing landscape in which CKR signaling is influenced by receptor PTMs, chemokine and CKR dimerization, and endogenous non-chemokine ligands. Simultaneous advances in the structural and functional characterization of 7TMR biased signaling have altered how we understand promiscuous chemokine-CKR interactions. In this review, we explore new paradigms in CKR signal transduction by considering studies that depict a more intricate architecture governing the consequences of chemokine-CKR interactions.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kleist, Andrew B.;  Medical College of Wisconsin > Department of Biochemistry
Getschman, Anthony E.
Ziarek, Joshua J.
Nevins, Amanda M.
Gauthier, Pierre-Arnaud ;  Université de Liège - ULiège > Doct. sc. (bioch., biol. mol.&cell., bioinf.&mod.-Bologne)
Chevigne, Andy
Szpakowska, Martyna
Volkman, Brian F.
Language :
English
Title :
New paradigms in chemokine receptor signal transduction: Moving beyond the two-site model.
Publication date :
19 April 2016
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Elsevier, Netherlands
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Published by Elsevier Inc.
Available on ORBi :
since 24 May 2016

Statistics


Number of views
40 (4 by ULiège)
Number of downloads
0 (0 by ULiège)

Scopus citations®
 
88
Scopus citations®
without self-citations
62
OpenCitations
 
95

Bibliography


Similar publications



Contact ORBi