Chemokines are small cytokines secreted by cells. They have ability to induce directed chemotaxis in nearby responsive cells. Chemokine families share structural characteristics such as 8-10 kilodaltons in size, and the presence of four cysteine residues in conserved locations. Chemokine exert their biological effects by interacting with G protein-linked transmembrane receptors called chemokine receptors. One of the members of chemokine families is CXC chemokines. Their first two cysteine residues are separated by one amino acid, represented in this name with an "X". Presently, there are 17 different CXC chemokines described in mammals. They bind to CXC chemokine receptors, of which seven have been identified to date, named CXCR1 to CXCR7. Chemokine ligand 14 (CXCL14) is a small cytokine belonging to the CXC chemokine family that is also known as BRAK (for breast and kidney-expressed chemokine). Mature CXCL14 has many of the conserved features of the CXC chemokine subfamily but has some differences too, such as a shorter N-terminus and five extra amino acids in the region between its third and fourth cysteines. CXCL14 is constitutively expressed at high levels in many normal tissues, where its cellular source is thought to be fibroblasts. However, it is reduced or absent from most cancer cells. This chemokine is chemotactic for monocytes and can activate these cells in the presence of an inflammatory mediator called prostaglandin-E2 (PGE2). It is also a potent chemoattractant and activator of dendritic cells, is implicated in homing of these cells, and can stimulate the migration of activated NK cells. CXCL14 also inhibits angiogenesis, possibly as a result of its ability to block endothelial cell chemotaxis. The gene for CXCL14 contains four exons and is located on chromosome 5 in humans. CXCL14 plays important roles in anti-cancer and immune system activation. However, the receptor of CXCL14 has not yet been identified. To bettrer understand the function and signal transduction pathway of CXCL14, the potential receptors for CXCL14 were studies. We confirmed that the known receptors for CXCL12, CXCR4, are also putative receptors for CXCL14 by using co-immunoprecipitation assays and receptor binding assay.
