CXCL16

  • OMIM: 605 ​​398
  • UniProt: Q9H2A7

CXCL16 (short for CXC motif chemokine 16, and scavenger receptor for phosphatidylserine and oxidized low density lipoprotein ( SR- PSOX ) ) is an endogenous neurotransmitter, which is assigned to the group of CXC motif chemokines. It has many unusual structural features, which distinguishes it from other chemokines. It occurs in both a membrane bound and a soluble form. As chemotactic acting, that is, the cell movement controlling, this peptide cytokine plays a role in the mobilization and targeted migration of T lymphocytes. This chemokine mediated its effects by binding to the chemokine receptor CXCR6. For CXCL16 and its receptor play a role in the development of atherosclerosis is accepted.

Occurrence

CXCL16 is a cell membrane -bound chemokine, which exists in particular at the surface of antigenic presenting cells such as B lymphocytes, macrophages and dendritic cells, and on cells of the splenic pulp. A soluble form of this chemokine in particular is released by macrophages.

Biochemistry

Genetics

CXCL16 is encoded by a gene on chromosome 17 locus p13. While many chemokines associated in specific gene regions occur, provides CXCL16 from a genetic point of view a loner represents the sequence of CXCL16 is less conserved across species than the other chemokines. There is a match of about 50 percent based on the amino acid sequence between human and mouse and pig on the one hand on the other hand.

Structure

CXCL16 combines unique structural features of CXC, CC, and CX3C chemokines. CXCL16 is composed of a chemokine, a mucin and transmembrane domain, a short intracellular C-terminus. The chemokine domain bears a characteristic CXC motif, which is why this chemokine was also classified in the group of CXC chemokines. In contrast, there is a higher amino acid sequence identity with the Chemokinmotivs resembles that of CC- chemokines and the modular design of the CX3C chemokine CX3CL1 ( fractalkine ).

CXCL16 is a protein which is subject to numerous post-translational modifications. The primary translation product with a molecular mass of about 28 kDa glycosylated or can be enzymatically cleaved. In membrane-bound, glycosylated form with a molecular mass of about 55 kDa is especially against CXCL16 on the cell surface of antigen-presenting cells. Under the influence of the metalloprotease ADAM10 may be cleaved from the membrane-bound form, a soluble variant with a molecular mass of 40 kDa.

Signal transduction

CXCL16 is both a adhesion and signaling molecule. It exerts its effects via binding and activation of occurring on the cell surface of T lymphocytes CXCR6 chemokine receptors. This receptor belongs to the family of G-protein - coupled receptors. After activation of the receptor, a transmission of the signal is carried into the cell interior via Gi protein, phosphoinositide 3 - kinases (PI3K ), the PIP3 -dependent kinase 1 ( PDK -1), the protein kinase B, the IkB - kinase and NF- kappa B. The signal transduction responsible for both the CXCL16 - mediated cell -cell adhesion as well as the proliferation-promoting effect of this chemokine in smooth muscle cells of the blood vessels.

Function

CXCL16 is particularly with the development of atherosclerosis is associated, this chemokine plays a multifunctional role as anti- and pro- atherosclerotic factor. Cell membrane- bound CXCL16 acts as a scavenger for apoptotic cells, phosphatidylserine and oxidized LDL cholesterol. Moreover, CXCL16 is a chemotactic effect on T-lymphocytes, promotes the adhesion to the endothelium of blood vessels and promotes cell proliferation and differentiation of smooth muscle cells in an inflammatory phenotype.

210450
de