Biology:CCL8

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Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Chemokine (C-C motif) ligand 8 (CCL8), also known as monocyte chemoattractant protein 2 (MCP2), is a protein that in humans is encoded by the CCL8 gene.[1][2]

CCL8 is a small cytokine belonging to the CC chemokine family. The CCL8 protein is produced as a precursor containing 109 amino acids, which is cleaved to produce mature CCL8 containing 75 amino acids. The gene for CCL8 is encoded by 3 exons and is located within a large cluster of CC chemokines on chromosome 17q11.2 in humans.[2][3] MCP-2 is chemotactic for and activates many different immune cells, including mast cells, eosinophils and basophils, (that are implicated in allergic responses), and monocytes, T cells, and NK cells that are involved in the inflammatory response.[4][5] CCL8 elicits its effects by binding to several different cell surface receptors called chemokine receptors. These receptors include CCR1, CCR2B, CCR3 and CCR5.[5][6]

CCL8 is a CC chemokine that utilizes multiple cellular receptors to attract and activate human leukocytes. CCL8 is a potent inhibitor of HIV1 by virtue of its high-affinity binding to the receptor CCR5, one of the major co-receptors for HIV1.[7] In addition, CCL8 attributes to the growth of metastasis in breast cancer cells. The manipulation of this chemokine activity influences the histology of tumors promoting steps of metastatic processes.[8] CCL8 is also involved in attracting macrophages to the decidua in labor.[9]

References

  1. ↑ "Entrez Gene: chemokine (C-C motif) ligand 8". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6355. 
  2. ↑ 2.0 2.1 "The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2". Genomics 40 (2): 323–31. March 1997. doi:10.1006/geno.1996.4594. PMID 9119400. 
  3. ↑ "Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family". J. Exp. Med. 176 (1): 59–65. July 1992. doi:10.1084/jem.176.1.59. PMID 1613466. 
  4. ↑ "Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1". J. Leukoc. Biol. 59 (1): 67–74. January 1996. doi:10.1002/jlb.59.1.67. PMID 8558070. 
  5. ↑ 5.0 5.1 "Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication". J. Biol. Chem. 273 (8): 4289–92. February 1998. doi:10.1074/jbc.273.8.4289. PMID 9468473. 
  6. ↑ "Functional expression of CCL8 and its interaction with chemokine receptor CCR3". BMC Immunol 18 (1): 54. 2017. doi:10.1186/s12865-017-0237-5. PMID 29281969. 
  7. ↑ PDB: 1ESR​; "Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors". Biochemistry 39 (46): 14075–81. November 2000. doi:10.1021/bi0009340. PMID 11087354. 
  8. ↑ "A CCL8 gradient drives breast cancer cell dissemination". Oncogene 35 (49): 6309–6318. 2016. doi:10.1038/onc.2016.161. PMID 27181207. 
  9. ↑ "Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour". PLOS ONE 8 (2): e56946. 2013. doi:10.1371/journal.pone.0056946. PMID 23451115. Bibcode: 2013PLoSO...856946H. 

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