CXC chemokine receptors
CXC chemokine receptors (CXCR) are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family.
They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors.
CXC chemokine receptors (CXCR) that are known as seven transmembrane (7-TM) proteins, since they span the cell membrane seven times.
There are currently six known CXC chemokine receptors: CXCR1 through CXCR6.
CXCR1 and CXCR2 are closely related receptors.
CXCR1 and CXCR2 recognize CXC chemokines that possess an E-L-R amino acid motif immediately adjacent to their CXC motif.
CXCL8 (interleukin-8) and CXCL6 can both bind CXCR1, while all other ELR-positive chemokines, such as CXCL1 to CXCL7 bind only CXCR2.
They are both expressed on the surface of neutrophils.
CXCR3 is expressed predominantly on T cells (T lymphocytes), and also on other lymphocytes [some B cells (B lymphocytes) and NK cells] and is highly induced following cell activation.
There are two isoforms, CXCR3-A and CXCR3-B.
It has three highly related ligands, CXCL9, CXCL10 and CXCL11.
CXCR4, also known as fusin, is the receptor for a chemokine known as CXCL12 (or SDF-1) and, as with CCR5, is utilized by HIV-1 to gain entry into target cells.
This receptor has a wide cellular distribution: on most immature and mature hematopoietic cell types (e.g. neutrophils, monocytes, T and B cells, dendritic cells, Langerhans cells and macrophages).
In addition, CXCR4 can also be found on vascular endothelial cells and neuronal cells.
The chemokine receptor CXCR5 is expressed on B cells and CD4+ Tfh cells and is involved in lymphocyte homing and the development of normal lymphoid tissue. Its principal ligand is CXCL13.
CXCR6 being assigned based on its chromosomal location within the chemokine receptor cluster on human chromosome 3p21) and its similarity to other chemokine receptors in its gene sequence.
CXCR6 binds the ligand CXCL16.
However, CXCR6 is more closely related in structure to CC chemokine receptors than to other CXC chemokine receptors.
CXCR4 (C-X-C chemokine receptor type 4) is a member of the G protein-coupled receptor (GPCR) superfamily.
It is also known as fusin or CD184.
CXCR4 specifically binds to the chemokine ligand CXCL12, also known as stromal cell-derived factor-1 (SDF-1), forming the CXCL12/CXCR4 axis.
This receptor is involved in various physiological processes, including hematopoiesis, organogenesis, and tissue repair.
It plays a critical role in cell proliferation, chemotaxis, migration, and gene expression.
CXCR4 is also implicated in the pathogenesis of several diseases, including HIV infection, inflammatory diseases, and various cancers such as breast cancer, gastric cancer, and non-small cell lung cancer.
In the context of cancer, the CXCL12/CXCR4 axis is known to contribute to tumor growth, survival, angiogenesis, metastasis, and therapeutic resistance.
Overexpression of CXCR4 in tumor tissues is associated with increased tumor aggressiveness and higher risks of metastasis and recurrence.
CXCR4 inhibitors being investigated in clinical trials for their potential anti-tumor activity.