title: Analysis of G Protein and β-Arrestin Activation in Chemokine Receptors Signaling.
abstract: 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.
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano, Milano, Italy; Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vacchini
authors.affiliation: CNR Institute of Neuroscience, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Busnelli
authors.affiliation: CNR Institute of Neuroscience, Milan, Italy.
authors.forename: Bice
authors.initials: B
authors.lastname: Chini
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano, Milano, Italy; Humanitas Clinical and Research Center, Rozzano, Italy. Electronic address: massimo.locati@humanitasresearch.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano, Milano, Italy; Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Elena Monica
authors.initials: EM
authors.lastname: Borroni
mesh_terms: D000818:Animals; D002460:Cell Line; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods; D008967:Molecular Biology / Q000379:methods*; D019707:Receptors, Chemokine / Q000378:metabolism*; D015398:Signal Transduction; D000071557:beta-Arrestins / Q000378:metabolism*
chemical_list: D019707:Receptors, Chemokine; D000071557:beta-Arrestins; D019204:GTP-Binding Proteins
keywords: Biased signaling; Chemokine; Chemokine receptors; G proteins; β-Arrestins