Chemokine receptors are classified into four subgroups, the CC chemokine receptors (CCRs), CXCRs, XCRs and CX3-CRs. In humans, 18 chemokine receptors, comprising 10 CCRs, 6CXCRs, 1 XCR, and 1 CX3CR, have been characterised and act as receptors for at least 44 chemokine ligands. The CXC receptor 1 and 2 (CXCR1 and CXCR2) have been well characterised in vertebrates. In mammals and birds, the two receptors are shared by the ELR+ CXC ligands, namely the CXCL8 family members that have proinflammatory roles in recruitment of neutrophils, monocytes and macrophages to sites of infection. Activation of CXCR1 and CXCR2 leads to a cascade of cellular events responsible for migration, homeostasis and adhesion of the target cells. CXCR1 primarily binds with CXCL6–8 whilst CXCR2 is less ligand specific, interacting with almost all of the ELR+ CXC chemokines including CXCL1–3 and CXCL5–8. CXCR1 and CXCR2 recruit GRK2 and GRK6 respectively, to regulate leucocyte functions. This can lead to functional differences. CXCR2 but not CXCR1 is involved in CXCL8 mediated angiogenesis and cancer growth.  CXCR3 is the sole receptor shared by three closely related ELR- chemokines CXCL9–11 and also interacts with CXCL4 and CCL21.  CXCR4 has been discovered as a single copy gene in agnathan and gnathostome vertebrates except for teleosts where duplicated CXCR4 (CXCR4a and4b), and their ligands CXCL12 (CXCL12a and 12b), are present.

References

1.Zou J,et al. Gen Comp Endocrinol. 2015 May 1;215:117-31.