Stromal cell-derived factor-1

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Chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)
250px
PDB rendering based on 1a15.
Available structures
PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB
Identifiers
Symbols CXCL12 ; PBSF; SCYB12; SDF-1a; SDF-1b; SDF1; SDF1A; SDF1B; TLSF-a; TLSF-b; TPAR1
External IDs OMIM: 600835 MGI103556 HomoloGene507
RNA expression pattern
File:PBB GE CXCL12 209687 at tn.png
File:PBB GE CXCL12 203666 at tn.png
More reference expression data
Orthologs

| | bgcolor="#C3FDB8" | Human | bgcolor="#C3FDB8" | Mouse |-

    | bgcolor="#C3FDB8" | Entrez 
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| 6387
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| 20315

|-

     | bgcolor="#C3FDB8" | Ensembl
     | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| ENSG00000107562
     | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| ENSMUSG00000061353

|-

    | bgcolor="#C3FDB8" | Uniprot
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| P48061
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| Q4FJL5

|-

    | bgcolor="#C3FDB8" | Refseq
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd" | NM_000609 (mRNA)
NP_000600 (protein)
| bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd" |NM_001012477 (mRNA)
NP_001012495 (protein)

|-

    | bgcolor="#C3FDB8" | Location
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"|  Chr 10: 44.19 - 44.2 Mb 
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"|  Chr 6: 117.13 -  117.15 Mb 

|-

|-

    | bgcolor="#C3FDB8" | Pubmed search 
    | bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| [1]
| bgcolor="#eeeeee" style="border-top:2px solid #dddddd; border-right:2px solid #dddddd"| [2]
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12).

For background information on chemokines, see CXCL11 (SCYB11; MIM 604852). Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the intercrine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF (see MIM 191160), or IL1 (see MIM 147760). The intercrines are characterized by the presence of 4 conserved cysteines which form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, which includes beta chemokine, the cysteine residues are adjacent to each other. In the CXC subfamily, which includes alpha chemokine, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group.[supplied by OMIM][1]

Structure

SDF-1 is produced in two forms, SDF-1α/CXCL12a and SDF-1β/CXCL12b, by alternate splicing of the same gene.[2] Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid.

Functions

Chemotaxis

CXCL12 is strongly chemotactic for lymphocytes.[3][4][5][6]

During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow and the formation of large blood vessels. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life.
In adulthood CXCL12 plays an important role in angoigenesis by recruiting endothelial progenitor cells (EPC) from the bone morrow through a CXCR4 dependent mechanism.[7] It is this function of CXCL12 that makes it a very important factor in carcinogenesis and the neovascularisation linked to tumour progression. [8]

Electrophysiology

As another role, CXCL12a alters also the electrophysiology of neurons.

Others

CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).

Receptor

The receptor for this chemokine is CXCR4, which was previously called fusin.[9] This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.[10][11]

Gene

The gene for CXCL12 is located on human chromosome 10.[12] In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

References

  1. "Entrez Gene: CXCL12 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)".
  2. De La Luz Sierra et al. Differential processing of stromal-derived factor-1alpha and beta explains functional diversity. Blood 103:2452-2459, 2004.
  3. Bleul et al. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J. Exp. Med. 184: 1101-1109, 1996.
  4. Ara et al. Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1). Proc. Nat. Acad. Sci. 100: 5319-5323, 2003.
  5. Askari et al. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362: 697-703, 2003.
  6. Ma et al. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc. Nat. Acad. Sci. 95: 9448-9453, 1998.
  7. Zheng H, Fu G, Dai T, Huang H. Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway.J Cardiovasc Pharmacol. 2007 Sep;50(3):274-80.Click here to read
  8. Kryczek I, Wei S, Keller E, Liu R, Zou W. Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis. Am J Physiol Cell Physiol. 2007 Mar;292(3):C987-95.
  9. Bleul et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382: 829-833, 1996.
  10. Balabanian et al. The chemokine SDF-1/CXCl12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem 280:35760-35766, 2005.
  11. Burns et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 203:2201-2213, 2006.
  12. Deloukas et al. The DNA sequence and comparative analysis of human chromosome 10. Nature 429:375-381, 2004.

Further reading

  • Kucia M, Reca R, Miekus K; et al. (2005). "Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis". Stem Cells. 23 (7): 879–94. doi:10.1634/stemcells.2004-0342. PMID 15888687.
  • Kryczek I, Wei S, Keller E; et al. (2007). "Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis". Am. J. Physiol., Cell Physiol. 292 (3): C987–95. doi:10.1152/ajpcell.00406.2006. PMID 16943240.
  • Stellos K, Gawaz M (2007). "Platelets and stromal cell-derived factor-1 in progenitor cell recruitment". Semin. Thromb. Hemost. 33 (2): 159–64. doi:10.1055/s-2007-969029. PMID 17340464.
  • Arya M, Ahmed H, Silhi N; et al. (2007). "Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer cell migration". Tumour Biol. 28 (3): 123–31. doi:10.1159/000102979. PMID 17510563.

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