TY - CHAP
T1 - Analysis of G Protein and β-Arrestin Activation in Chemokine Receptors Signaling
AU - Vacchini, Alessandro
AU - Busnelli, Marta
AU - Chini, Bice
AU - Locati, Massimo
AU - Borroni, Elena Monica
PY - 2016
Y1 - 2016
N2 - Chemokines are key regulators of leukocyte migration and play fundamental roles in immune responses. The chemokine system includes a set of over 40 ligands which engage in a promiscuous fashion a panel of over 25 receptors belonging to a distinct family of 7 transmembrane-domain receptors (7TM) widely expressed on a variety of cells. Although responses evoked by chemokine receptors have long been considered the result of balanced activation of the G protein- and β-arrestin-dependent signaling modules, evidence is accumulating showing that these receptors are capable, as other 7TMs, to activate different signaling modules in a ligand- and cell/tissue-specific manner. This biased signaling, or functional selectivity, confers a hitherto largely uncharacterized level of complexity to the chemokine system and challenges our present understanding of its redundancy. At the same time, it also provides new insights of relevance for chemokine receptors targeting drug development plans. Here, we provide current methods to study biased signaling of chemokine receptors by dissecting G proteins and β-arrestins activation upon chemokine stimulation.
AB - Chemokines are key regulators of leukocyte migration and play fundamental roles in immune responses. The chemokine system includes a set of over 40 ligands which engage in a promiscuous fashion a panel of over 25 receptors belonging to a distinct family of 7 transmembrane-domain receptors (7TM) widely expressed on a variety of cells. Although responses evoked by chemokine receptors have long been considered the result of balanced activation of the G protein- and β-arrestin-dependent signaling modules, evidence is accumulating showing that these receptors are capable, as other 7TMs, to activate different signaling modules in a ligand- and cell/tissue-specific manner. This biased signaling, or functional selectivity, confers a hitherto largely uncharacterized level of complexity to the chemokine system and challenges our present understanding of its redundancy. At the same time, it also provides new insights of relevance for chemokine receptors targeting drug development plans. Here, we provide current methods to study biased signaling of chemokine receptors by dissecting G proteins and β-arrestins activation upon chemokine stimulation.
KW - Biased signaling
KW - Chemokine
KW - Chemokine receptors
KW - G proteins
KW - β-Arrestins
UR - http://www.scopus.com/inward/record.url?scp=84959110787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959110787&partnerID=8YFLogxK
U2 - 10.1016/bs.mie.2015.09.016
DO - 10.1016/bs.mie.2015.09.016
M3 - Chapter
AN - SCOPUS:84959110787
VL - 570
T3 - Methods in Enzymology
SP - 421
EP - 440
BT - Methods in Enzymology
PB - Academic Press Inc.
ER -