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Gene Review

CXCL12  -  chemokine (C-X-C motif) ligand 12

Homo sapiens

Synonyms: C-X-C motif chemokine 12, IRH, Intercrine reduced in hepatomas, PBSF, Pre-B cell growth-stimulating factor, ...
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Disease relevance of CXCL12


Psychiatry related information on CXCL12


High impact information on CXCL12


Chemical compound and disease context of CXCL12


Biological context of CXCL12


Anatomical context of CXCL12


Associations of CXCL12 with chemical compounds


Physical interactions of CXCL12


Enzymatic interactions of CXCL12

  • A mutant SDF-1 that does not interact with HS is readily cleaved by DPP IV, a process that is not inhibited by HS, demonstrating that a productive interaction between HS and SDF-1 is required for the protection to take place [34].
  • Moreover, tyrosine-phosphorylated syndecan-4 from CXCL12-stimulated HeLa cells physically coassociates with tyrosine phosphorylated CXCR4 [35].
  • Immunocytochemistry confirmed SDF-1-induced nuclear translocation of phosphorylated ERK1/2 [36].
  • Matrix metalloproteinase (MMP)-2 cleaves the 4 amino-terminal residues of the chemokine, stromal cell-derived factor (SDF)-1alpha, yielding a highly neurotoxic molecule, SDF(5-67), which fails to bind to its cognate receptor, CXCR4 [37].
  • The objective of this study was to investigate whether or not cross-linking ICAM-1 on the surface of airway epithelial cells phosphorylated MAP kinases or stimulated chemokine expression and secretion [38].

Co-localisations of CXCL12


Regulatory relationships of CXCL12


Other interactions of CXCL12

  • Consistent with this discrepancy, two distinct chemokine receptors, namely, CXCR4 (ref. 7) and CCR5 (ref. 8), were recently identified as potential co-receptors for T-cell line-adapted and macrophage-tropic HIV-1 isolates, respectively [20].
  • Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression [49].
  • Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES [50].
  • Several members of the chemokine receptor family have been shown to function in association with CD4 to permit human immunodeficiency virus type 1 (HIV-1) entry and infection [51].
  • Because pDCs express both the lymph node homing molecule l-selectin and the cutaneous homing molecule cutaneous lymphocyte antigen, the cooperation between inducible CXCR3 ligands and constitutive SDF-1/CXCL12 may regulate recruitment of pDCs either in lymph nodes or at peripheral sites of inflammation [42].

Analytical, diagnostic and therapeutic context of CXCL12


  1. Involvement of chemokine receptors in breast cancer metastasis. Müller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M.E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S.N., Barrera, J.L., Mohar, A., Verástegui, E., Zlotnik, A. Nature (2001) [Pubmed]
  2. Chemokine receptor expression in EBV-associated lymphoproliferation in hu/SCID mice: implications for CXCL12/CXCR4 axis in lymphoma generation. Piovan, E., Tosello, V., Indraccolo, S., Cabrelle, A., Baesso, I., Trentin, L., Zamarchi, R., Tamamura, H., Fujii, N., Semenzato, G., Chieco-Bianchi, L., Amadori, A. Blood (2005) [Pubmed]
  3. Involvement of CXCR4 and IL-2 in the homing and retention of human NK and NK T cells to the bone marrow and spleen of NOD/SCID mice. Beider, K., Nagler, A., Wald, O., Franitza, S., Dagan-Berger, M., Wald, H., Giladi, H., Brocke, S., Hanna, J., Mandelboim, O., Darash-Yahana, M., Galun, E., Peled, A. Blood (2003) [Pubmed]
  4. Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Burger, M., Hartmann, T., Krome, M., Rawluk, J., Tamamura, H., Fujii, N., Kipps, T.J., Burger, J.A. Blood (2005) [Pubmed]
  5. Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome. Gulino, A.V., Moratto, D., Sozzani, S., Cavadini, P., Otero, K., Tassone, L., Imberti, L., Pirovano, S., Notarangelo, L.D., Soresina, R., Mazzolari, E., Nelson, D.L., Notarangelo, L.D., Badolato, R. Blood (2004) [Pubmed]
  6. CXCL12 G801A polymorphism is a risk factor for sporadic prostate cancer susceptibility. Hirata, H., Hinoda, Y., Kikuno, N., Kawamoto, K., Dahiya, A.V., Suehiro, Y., Tanaka, Y., Dahiya, R. Clin. Cancer Res. (2007) [Pubmed]
  7. Plasma stromal cell-derived factor-1: host derived marker predictive of distant metastasis in breast cancer. Hassan, S., Baccarelli, A., Salvucci, O., Basik, M. Clin. Cancer Res. (2008) [Pubmed]
  8. Human immunodeficiency virus-1 entry into purified blood dendritic cells through CC and CXC chemokine coreceptors. Ayehunie, S., Garcia-Zepeda, E.A., Hoxie, J.A., Horuk, R., Kupper, T.S., Luster, A.D., Ruprecht, R.M. Blood (1997) [Pubmed]
  9. Lymphotropic virions affect chemokine receptor-mediated neural signaling and apoptosis: implications for human immunodeficiency virus type 1-associated dementia. Zheng, J., Ghorpade, A., Niemann, D., Cotter, R.L., Thylin, M.R., Epstein, L., Swartz, J.M., Shepard, R.B., Liu, X., Nukuna, A., Gendelman, H.E. J. Virol. (1999) [Pubmed]
  10. Chemokines/chemokine receptors in the central nervous system and Alzheimer's disease. Xia, M.Q., Hyman, B.T. J. Neurovirol. (1999) [Pubmed]
  11. Involvement of cytokines in human immunodeficiency virus-1 protein Tat and methamphetamine interactions in the striatum. Theodore, S., Cass, W.A., Maragos, W.F. Exp. Neurol. (2006) [Pubmed]
  12. Characterization of chemokine receptors expressed in primitive blood cells during human hematopoietic ontogeny. Rosu-Myles, M., Khandaker, M., Wu, D.M., Keeney, M., Foley, S.R., Howson-Jan, K., Yee, I.C., Fellows, F., Kelvin, D., Bhatia, M. Stem Cells (2000) [Pubmed]
  13. B CELL IMMUNOBIOLOGY IN DISEASE: Evolving Concepts from the Clinic. Martin, F., Chan, A.C. Annu. Rev. Immunol. (2006) [Pubmed]
  14. Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Cyster, J.G. Annu. Rev. Immunol. (2005) [Pubmed]
  15. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Rot, A., von Andrian, U.H. Annu. Rev. Immunol. (2004) [Pubmed]
  16. Epithelial cancer cell migration: a role for chemokine receptors? Scotton, C.J., Wilson, J.L., Milliken, D., Stamp, G., Balkwill, F.R. Cancer Res. (2001) [Pubmed]
  17. The chemokine stromal cell derived factor-1 (CXCL12) promotes glioma invasiveness through MT2-matrix metalloproteinase. Zhang, J., Sarkar, S., Yong, V.W. Carcinogenesis (2005) [Pubmed]
  18. Up-regulation of functional CXCR4 expression on human lymphocytes in sepsis. Ding, Z., Jia, S.H., Marshall, J.C., Downey, G.P., Waddell, T.K. Crit. Care Med. (2006) [Pubmed]
  19. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Krumbholz, M., Theil, D., Cepok, S., Hemmer, B., Kivisäkk, P., Ransohoff, R.M., Hofbauer, M., Farina, C., Derfuss, T., Hartle, C., Newcombe, J., Hohlfeld, R., Meinl, E. Brain (2006) [Pubmed]
  20. The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Cocchi, F., DeVico, A.L., Garzino-Demo, A., Cara, A., Gallo, R.C., Lusso, P. Nat. Med. (1996) [Pubmed]
  21. Lck is required for stromal cell-derived factor 1 alpha (CXCL12)-induced lymphoid cell chemotaxis. Inngjerdingen, M., Torgersen, K.M., Maghazachi, A.A. Blood (2002) [Pubmed]
  22. Activation of Vav/Rho GTPase signaling by CXCL12 controls membrane-type matrix metalloproteinase-dependent melanoma cell invasion. Bartolomé, R.A., Molina-Ortiz, I., Samaniego, R., Sánchez-Mateos, P., Bustelo, X.R., Teixidó, J. Cancer Res. (2006) [Pubmed]
  23. Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4. Marchesi, F., Monti, P., Leone, B.E., Zerbi, A., Vecchi, A., Piemonti, L., Mantovani, A., Allavena, P. Cancer Res. (2004) [Pubmed]
  24. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. Broxmeyer, H.E., Orschell, C.M., Clapp, D.W., Hangoc, G., Cooper, S., Plett, P.A., Liles, W.C., Li, X., Graham-Evans, B., Campbell, T.B., Calandra, G., Bridger, G., Dale, D.C., Srour, E.F. J. Exp. Med. (2005) [Pubmed]
  25. Stromal cell-derived factor-1alpha/CXCL12-induced chemotaxis of T cells involves activation of the RasGAP-associated docking protein p62Dok-1. Okabe, S., Fukuda, S., Kim, Y.J., Niki, M., Pelus, L.M., Ohyashiki, K., Pandolfi, P.P., Broxmeyer, H.E. Blood (2005) [Pubmed]
  26. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Burger, J.A., Kipps, T.J. Blood (2006) [Pubmed]
  27. Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas. Trentin, L., Cabrelle, A., Facco, M., Carollo, D., Miorin, M., Tosoni, A., Pizzo, P., Binotto, G., Nicolardi, L., Zambello, R., Adami, F., Agostini, C., Semenzato, G. Blood (2004) [Pubmed]
  28. MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by {alpha}4beta1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration. Redondo-Mu??oz, J., Escobar-D??az, E., Samaniego, R., Terol, M.J., Garc??a-Marco, J.A., Garc??a-Pardo, A. Blood (2006) [Pubmed]
  29. H4 histamine receptor mediates optimal migration of mast cell precursors to CXCL12. Godot, V., Arock, M., Garcia, G., Capel, F., Flys, C., Dy, M., Emilie, D., Humbert, M. J. Allergy Clin. Immunol. (2007) [Pubmed]
  30. CCR5-binding chemokines modulate CXCL12 (SDF-1)-induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor. Honczarenko, M., Le, Y., Glodek, A.M., Majka, M., Campbell, J.J., Ratajczak, M.Z., Silberstein, L.E. Blood (2002) [Pubmed]
  31. Opposite effects of SDF-1 on human immunodeficiency virus type 1 replication. Maréchal, V., Arenzana-Seisdedos, F., Heard, J.M., Schwartz, O. J. Virol. (1999) [Pubmed]
  32. The human erythrocyte inflammatory peptide (chemokine) receptor. Biochemical characterization, solubilization, and development of a binding assay for the soluble receptor. Horuk, R., Colby, T.J., Darbonne, W.C., Schall, T.J., Neote, K. Biochemistry (1993) [Pubmed]
  33. Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils. White, J.R., Imburgia, C., Dul, E., Appelbaum, E., O'Donnell, K., O'Shannessy, D.J., Brawner, M., Fornwald, J., Adamou, J., Elshourbagy, N.A., Kaiser, K., Foley, J.J., Schmidt, D.B., Johanson, K., Macphee, C., Moores, K., McNulty, D., Scott, G.F., Schleimer, R.P., Sarau, H.M. J. Leukoc. Biol. (1997) [Pubmed]
  34. Heparan sulfate/heparin oligosaccharides protect stromal cell-derived factor-1 (SDF-1)/CXCL12 against proteolysis induced by CD26/dipeptidyl peptidase IV. Sadir, R., Imberty, A., Baleux, F., Lortat-Jacob, H. J. Biol. Chem. (2004) [Pubmed]
  35. Syndecan-4 is a signaling molecule for stromal cell-derived factor-1 (SDF-1)/ CXCL12. Charnaux, N., Brule, S., Hamon, M., Chaigneau, T., Saffar, L., Prost, C., Lievre, N., Gattegno, L. FEBS J. (2005) [Pubmed]
  36. Stromal cell-derived factor-1 (SDF-1) signalling regulates human placental trophoblast cell survival. Jaleel, M.A., Tsai, A.C., Sarkar, S., Freedman, P.V., Rubin, L.P. Mol. Hum. Reprod. (2004) [Pubmed]
  37. Proteolytic processing of SDF-1{alpha} reveals a change in receptor specificity mediating HIV-associated neurodegeneration. Vergote, D., Butler, G.S., Ooms, M., Cox, J.H., Silva, C., Hollenberg, M.D., Jhamandas, J.H., Overall, C.M., Power, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  38. Selective regulation of MAP kinases and chemokine expression after ligation of ICAM-1 on human airway epithelial cells. Krunkosky, T.M., Jarrett, C.L. Respir. Res. (2006) [Pubmed]
  39. Matrix metalloproteinase-1 produced by human CXCL12-stimulated natural killer cells. Goda, S., Inoue, H., Umehara, H., Miyaji, M., Nagano, Y., Harakawa, N., Imai, H., Lee, P., Macarthy, J.B., Ikeo, T., Domae, N., Shimizu, Y., Iida, J. Am. J. Pathol. (2006) [Pubmed]
  40. CXCR4 and SDF1 expression in human meningiomas: A proliferative role in tumoral meningothelial cells in vitro. Bajetto, A., Barbieri, F., Pattarozzi, A., Dorcaratto, A., Porcile, C., Ravetti, J.L., Zona, G., Spaziante, R., Schettini, G., Florio, T. Neuro-oncology (2007) [Pubmed]
  41. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Oberlin, E., Amara, A., Bachelerie, F., Bessia, C., Virelizier, J.L., Arenzana-Seisdedos, F., Schwartz, O., Heard, J.M., Clark-Lewis, I., Legler, D.F., Loetscher, M., Baggiolini, M., Moser, B. Nature (1996) [Pubmed]
  42. The inducible CXCR3 ligands control plasmacytoid dendritic cell responsiveness to the constitutive chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12. Vanbervliet, B., Bendriss-Vermare, N., Massacrier, C., Homey, B., de Bouteiller, O., Brière, F., Trinchieri, G., Caux, C. J. Exp. Med. (2003) [Pubmed]
  43. Chemokine expression by systemic sclerosis fibroblasts: abnormal regulation of monocyte chemoattractant protein 1 expression. Galindo, M., Santiago, B., Rivero, M., Rullas, J., Alcami, J., Pablos, J.L. Arthritis Rheum. (2001) [Pubmed]
  44. A potential immune escape mechanism by melanoma cells through the activation of chemokine-induced T cell death. Mellado, M., de Ana, A.M., Moreno, M.C., Martínez, C., Rodríguez-Frade, J.M. Curr. Biol. (2001) [Pubmed]
  45. Circulating CD26 is negatively associated with inflammation in human and experimental arthritis. Busso, N., Wagtmann, N., Herling, C., Chobaz-Péclat, V., Bischof-Delaloye, A., So, A., Grouzmann, E. Am. J. Pathol. (2005) [Pubmed]
  46. Up-regulation of stromal cell-derived factor 1 (CXCL12) production in rheumatoid synovial fibroblasts through interactions with T lymphocytes: role of interleukin-17 and CD40L-CD40 interaction. Kim, K.W., Cho, M.L., Kim, H.R., Ju, J.H., Park, M.K., Oh, H.J., Kim, J.S., Park, S.H., Lee, S.H., Kim, H.Y. Arthritis Rheum. (2007) [Pubmed]
  47. Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas. Barbieri, F., Bajetto, A., Stumm, R., Pattarozzi, A., Porcile, C., Zona, G., Dorcaratto, A., Ravetti, J.L., Minuto, F., Spaziante, R., Schettini, G., Ferone, D., Florio, T. Clin. Cancer Res. (2008) [Pubmed]
  48. Reduced activation of protein kinase B, Rac, and F-actin polymerization contributes to an impairment of stromal cell derived factor-1 induced migration of CD34+ cells from patients with myelodysplasia. Fuhler, G.M., Drayer, A.L., Olthof, S.G., Schuringa, J.J., Coffer, P.J., Vellenga, E. Blood (2008) [Pubmed]
  49. Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression. Mummidi, S., Ahuja, S.S., Gonzalez, E., Anderson, S.A., Santiago, E.N., Stephan, K.T., Craig, F.E., O'Connell, P., Tryon, V., Clark, R.A., Dolan, M.J., Ahuja, S.K. Nat. Med. (1998) [Pubmed]
  50. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Scarlatti, G., Tresoldi, E., Björndal, A., Fredriksson, R., Colognesi, C., Deng, H.K., Malnati, M.S., Plebani, A., Siccardi, A.G., Littman, D.R., Fenyö, E.M., Lusso, P. Nat. Med. (1997) [Pubmed]
  51. A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. Murakami, T., Nakajima, T., Koyanagi, Y., Tachibana, K., Fujii, N., Tamamura, H., Yoshida, N., Waki, M., Matsumoto, A., Yoshie, O., Kishimoto, T., Yamamoto, N., Nagasawa, T. J. Exp. Med. (1997) [Pubmed]
  52. ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL). Richardson, S.J., Matthews, C., Catherwood, M.A., Alexander, H.D., Carey, B.S., Farrugia, J., Gardiner, A., Mould, S., Oscier, D., Copplestone, J.A., Prentice, A.G. Blood (2006) [Pubmed]
  53. Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Zou, L., Barnett, B., Safah, H., Larussa, V.F., Evdemon-Hogan, M., Mottram, P., Wei, S., David, O., Curiel, T.J., Zou, W. Cancer Res. (2004) [Pubmed]
  54. Human first-trimester trophoblast cells recruit CD56brightCD16- NK cells into decidua by way of expressing and secreting of CXCL12/stromal cell-derived factor 1. Wu, X., Jin, L.P., Yuan, M.M., Zhu, Y., Wang, M.Y., Li, D.J. J. Immunol. (2005) [Pubmed]
  55. Activating and inhibitory Ly49 receptors modulate NK cell chemotaxis to CXC chemokine ligand (CXCL) 10 and CXCL12. Inngjerdingen, M., Rolstad, B., Ryan, J.C. J. Immunol. (2003) [Pubmed]
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