Pathways & interactions
CXC chemokine receptor 7 (IPR001416)
Short name: Chemokine_CXCR7
Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role [PMID: 11544102]. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [PMID: 9689100], and endothelial cells, where they may act as either angiogenic or angiostatic factors [PMID: 7592998].
The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).
Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors [PMID: 10714678]. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [PMID: 10601351, PMID: 9500790]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).
This entry represents CXC chemokine receptor 7 (CXCR7) it causes chemotaxis in T lymphocytes in response to CXCL12 (SDF1) [PMID: 16107333]. CXCR7 can also bind CXCL11 [PMID: 16940167], which is an established ligand for CXCR3 [PMID: 22989616]. CXCR7 has been given chemokine receptor status from the International Union of Basic and Clinical Pharmacology (IUPHAR) but it has been subsequently shown that unlike other CXC chemokine receptors, CXCR7 does not elicit classical chemokine receptor signalling via typical G protein-mediated pathways [PMID: 20018651], but instead induces beta-arrestin recruitment, leading to ligand internalisation and activation of MAPK signaling pathway [PMID: 19641136, PMID: 20018651]. CXCR7 is therefore regarded as acting as a scavenger for CXCL12 and, to a lesser extent, for CXCL11 [PMID: 20161793].
CXCR7 has been identified on memory B cells and in mammals is found in bone, brain, heart and kidney [PMID: 18442043, PMID: 17804806]. It has been shown to act as a novel coreceptor for several immunodeficiency virus strains, which infect brain-derived cells [PMID: 10623723]. Studies of reduced CXCR7 expression in zebrafish have also revealled a critical role in vascular formation and angiogenesis during development [PMID: 17898181]. CXCR7 has also been shown to promote growth of tumors formed from breast and lung cancer cells [PMID: 16940167].
- PR00646 (RDC1ORPHANR)