Probing Biased Signaling in Chemokine Receptors

Roxana Maria Amarandi, Gertrud Malene Hjortø, Mette Marie Rosenkilde, Stefanie Karlshøj*

*Corresponding author for this work
    13 Citations (Scopus)

    Abstract

    The chemokine system mediates leukocyte migration during homeostatic and inflammatory processes. Traditionally, it is described as redundant and promiscuous, with a single chemokine ligand binding to different receptors and a single receptor having several ligands. Signaling of chemokine receptors occurs via two major routes, G protein- and β-arrestin-dependent, which can be preferentially modulated depending on the ligands or receptors involved, as well as the cell types or tissues in which the signaling event occurs. The preferential activation of a certain signaling pathway to the detriment of others has been termed signaling bias and can accordingly be grouped into ligand bias, receptor bias, and tissue bias. Bias has so far been broadly overlooked in the process of drug development. The low number of currently approved drugs targeting the chemokine system, as well as the broad range of failed clinical trials, reflects the need for a better understanding of the chemokine system. Thus, understanding the character, direction, and consequence of biased signaling in the chemokine system may aid the development of new therapeutics. This review describes experiments to assess G protein-dependent and -independent signaling in order to quantify chemokine system bias.

    Original languageEnglish
    Title of host publicationMethods in Enzymology
    Number of pages32
    Volume570
    PublisherAcademic Press
    Publication date2016
    Pages155-186
    DOIs
    Publication statusPublished - 2016
    SeriesMethods in Enzymology
    Volume570
    ISSN0076-6879

    Keywords

    • 7TMR
    • Bias
    • cAMP
    • Chemokine system
    • Chemotaxis
    • ERK
    • GPCR
    • GTPγS
    • Internalization
    • IP
    • β-Arrestin

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