Probing Biased Signaling in Chemokine Receptors
Research output: Chapter in Book/Report/Conference proceeding › Book chapter › Research › peer-review
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Probing Biased Signaling in Chemokine Receptors. / Amarandi, Roxana Maria; Hjortø, Gertrud Malene; Rosenkilde, Mette Marie; Karlshøj, Stefanie.
Methods in Enzymology. Vol. 570 Academic Press, 2016. p. 155-186 (Methods in Enzymology, Vol. 570).Research output: Chapter in Book/Report/Conference proceeding › Book chapter › Research › peer-review
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TY - CHAP
T1 - Probing Biased Signaling in Chemokine Receptors
AU - Amarandi, Roxana Maria
AU - Hjortø, Gertrud Malene
AU - Rosenkilde, Mette Marie
AU - Karlshøj, Stefanie
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - 7TMR
KW - Bias
KW - cAMP
KW - Chemokine system
KW - Chemotaxis
KW - ERK
KW - GPCR
KW - GTPγS
KW - Internalization
KW - IP
KW - β-Arrestin
U2 - 10.1016/bs.mie.2015.09.001
DO - 10.1016/bs.mie.2015.09.001
M3 - Book chapter
C2 - 26921946
AN - SCOPUS:84959084638
VL - 570
T3 - Methods in Enzymology
SP - 155
EP - 186
BT - Methods in Enzymology
PB - Academic Press
ER -
ID: 179052256