Chemokine Receptor

Chemokine receptors are GPCRs—integral membrane proteins composed of seven transmembrane helical segments. Different subsets of leukocytes express different arrays of chemokine receptors enabling them to respond to the appropriate ligands. Upon binding to their cognate chemokine ligands, the receptors undergo conformational changes giving rise to activation of intracellular effectors (G proteins or β-arrestins), initiation of signal transduction pathways and, ultimately, cellular responses. Mammalian genomes each encode approximately 20 chemokine receptors. Because the receptors were discovered after the chemokines and most of them are selective for members of one chemokine subfamily, they are classified according to the subfamily of chemokines to which most of their ligands belong. Thus, receptors are named using the prefixes CCR, CXCR, CX3CR, and XCR followed by an identifying number. 
Upon activation, GPCRs function as guanine nucleotide exchange factors (GEFs), which allows the α subunit of the heterotrimeric G protein to transition from inactive (GDP-bound) to active (GTP-bound) and to dissociate from the βγ subunits. Gβγ can regulate ion channels and is also involved in phosphorylation of the extracellular signal-regulated kinases (ERK 1/2) via the protein kinase C/protein kinase A pathway. The arrestin family also includes four subtypes. Arrestin-1 (visual arrestin) and arrestin-4 (cone arrestin) are located exclusively in retinal rods and cones. Arrestin-2 (or β-arrestin 1) and arrestin-3 (or β-arrestin 2) are non-visual arrestins that are expressed in numerous cell types. G protein-independent β-arrestin mediated signaling is less well characterized, but it has been identified using GPCR mutants unable to bind to G proteins, which are still able to signal through the ERK phosphorylation pathway.


1.Stone MJ,et al. Int J Mol Sci. 2017 Feb 7;18(2). pii: E342.