CXCL16

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CXCL16
Properties of human protein
Mass / length primary structure 254 AS ; 27.6  kDa
Identifier
Gene names CXCL16  ; SCYB16; SRPSOX
External IDs
Occurrence
Homology family Small inducible cytokines
Parent taxon Vertebrates

CXCL16 (short for CXC-Motiv-Chemokine 16 , also Scavenger receptor for phosphatidylserine and oxidized low density lipoprotein (SR-PSOX) ) is an endogenous messenger substance, which is assigned to the group of CXC-Motiv chemokines . It has numerous unusual structural properties that distinguish it from other chemokines. It occurs both bound in a cell membrane and in a soluble form. As a chemotactic cytokine , that is, it controls cell movement , this peptide plays a role in the mobilization and targeted migration of T lymphocytes . This chemokine mediates its effects by binding to the chemokine receptor CXCR6 . CXCL16 and its receptor are believed to play a role in the development of arteriosclerosis .

Occurrence

CXCL16 is a cell membrane-bound chemokine that occurs in particular on the surface of antigen-representing cells such as B-lymphocytes , macrophages and dendritic cells , as well as on cells of the spleen pulp . A soluble variant of this chemokine is released in particular by macrophages.

biochemistry

genetics

CXCL16 is encoded by a gene on chromosome 17 gene locus p13. While many chemokines occur together in certain gene regions, CXCL16 is a loner from a genetic point of view. The sequence of CXCL16 is less conserved across species than that of other chemokines. Between humans on the one hand and mouse or pig on the other hand there is a correspondence of about 50 percent based on the amino acid sequence.

structure

CXCL16 combines unique structural features of CXC, CC and CX 3 C chemokines. CXCL16 consists of a chemokine, a mucin and a transmembrane domain with a short intracellular C-terminus. The chemokine domain bears a characteristic CXC motif, which is why this chemokine has also been classified in the group of CXC chemokines. In contrast, there is a higher amino acid sequence match between the chemokine motif and that of CC chemokines and the modular structure is similar to the CX 3 C chemokine CX 3 CL1 (fractalkin).

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

Signal forwarding

On the one hand, CXCL16 is an adhesion and signaling molecule. It mediates its effects by binding and activating the chemokine receptors CXCR6 that occur on the cell surface of T lymphocytes. This receptor belongs to the family of G protein-coupled receptors . After activation of the receptor, the signal is passed on into the cell interior via G i proteins , phosphoinositide 3 kinases (PI3K), PIP3 dependent kinase 1 (PDK 1), protein kinase B , IκB kinase and NF -κB . This signal transduction mechanism is responsible for the CXCL16-mediated cell-cell adhesion as well as for the proliferation-promoting effect of this chemokine on cells of the smooth muscles of the blood vessels .

function

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

Individual evidence

  1. ↑ a b c Matloubian M, David A, Angel S, Ryan JE, JG Cyster: A transmembrane CXC chemokine is a ligand for HIV coreceptor Bonzo . In: Nat. Immunol. . 1, No. 4, October 2000, pp. 298-304. doi : 10.1038 / 79738 . PMID 11017100 .
  2. ↑ Shimaoka T, Kume N, Minami M, et al. : Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages . In: J. Biol. Chem. . 275, No. 52, December 2000, pp. 40663-6. doi : 10.1074 / jbc.C000761200 . PMID 11060282 .
  3. ↑ Wilbanks A, Zondlo SC, Murphy K, et al. : Expression cloning of the STRL33 / BONZO / TYMSTR ligand reveals elements of CC, CXC, and CX3C chemokines . In: J. Immunol. . 166, No. 8, April 2001, pp. 5145-54. PMID 11290797 .
  4. ↑ Gough PJ, Garton KJ, Wille PT, Rychlewski M, Dempsey PJ, Raines EW: A disintegrin and metalloproteinase 10-mediated cleavage and shedding regulates the cell surface expression of CXC chemokine ligand 16 . In: J. Immunol. . 172, No. 6, March 2004, pp. 3678-85. PMID 15004171 .
  5. ↑ a b Chandrasekar B, Bysani S, Mummidi S: CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation . In: J. Biol. Chem. . 279, No. 5, January 2004, pp. 3188-96. doi : 10.1074 / jbc.M311660200 . PMID 14625285 .
  6. ↑ Ludwig A, Weber C: Transmembrane chemokines: versatile 'special agents' in vascular inflammation . In: Thromb. Haemost. . 97, No. 5, May 2007, pp. 694-703. PMID 17479179 .
  7. ↑ Sheikine Y, Sirsjö A: CXCL16 / SR-PSOX - a friend or a foe in atherosclerosis? . In: Atherosclerosis . 197, No. 2, April 2008, pp. 487-95. doi : 10.1016 / j.atherosclerosis.2007.11.034 . PMID 18191863 .