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Gene Review

Kitl  -  kit ligand

Mus musculus

Synonyms: Clo, Con, Gb, Hematopoietic growth factor KL, Kit ligand, ...
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Disease relevance of Kitl


Psychiatry related information on Kitl

  • These data suggest that interaction of SCF with the c-kit receptor affects the homing behavior of hematopoietic progenitor cells in the adult animal [6].
  • We demonstrate that survival of a melanogenic subpopulation of cultured murine crest cells requires SLF for a critical period, which begins only after the second day of dispersal in vitro [7].
  • Genetically engineered mice lacking HGF/SF die in utero due to a failure of placental and hepatocyte differentiation, but little information exists regarding the expression of this signaling system in human development [8].
  • The altered AChE glycosylation was due to an increase in a minor AChE isoform, which did not bind Con A, similar to that previously observed to be increased in Alzheimer's disease brain and cerebrospinal fluid [9].
  • It has previously been shown that immunization with pathogenic anti-DNA idiotypes (Ids; e.g. 16/6 Id) leads to the induction of experimental system lupus erythematosus (SLF) in naive mice [10].

High impact information on Kitl

  • Assembly of this SCF complex is regulated by cell-cycle-dependent phosphorylation of NIPA, which restricts substrate ubiquitination activity to interphase [11].
  • Kit/SCF signaling and Mitf-dependent transcription are both essential for melanocyte development and pigmentation [12].
  • Matrix metalloproteinase-9 (MMP-9), induced in BM cells, releases soluble Kit-ligand (sKitL), permitting the transfer of endothelial and hematopoietic stem cells (HSCs) from the quiescent to proliferative niche [13].
  • To examine the function of SCF-induced phosphatidylinositol (PI) 3'-kinase activation in vivo, we employed the Cre-loxP system to mutate the codon for Tyr719, the PI 3'-kinase binding site in Kit/SCF-R, to Phe in the genome of mice by homologous recombination [14].
  • Receptor dimerization is ubiquitous to the action of all receptor tyrosine kinases, and in the case of dimeric ligands, such as the stem cell factor (SCF), it was attributed to ligand bivalency [15].

Chemical compound and disease context of Kitl


Biological context of Kitl


Anatomical context of Kitl


Associations of Kitl with chemical compounds

  • Thus the C-terminal valine defines a specific ER export signal in Kitl [25].
  • Kitl-stimulated testosterone production was 2-fold higher than that in untreated controls [23].
  • By comparing the effects of multiple Kitl mutations, including two N-ethyl-N-nitrosourea-induced hypomorphic mutations, we were able to distinguish stages of PGC development that are preferentially affected by certain mutations [26].
  • Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor [1].
  • But labelling with bromodeoxyuridine shows that SCF is not, by itself, a mitogen for PGC [27].

Physical interactions of Kitl

  • In addition, our current understanding of the molecular basis of various Steel and Dominant Spotting alleles coupled with the emerging information on the expression pattern of steel factor and c-kit transcripts during development, is now beginning to explain the pleiotropic affects of these mutations [28].
  • Epo stimulation of BMMCs led to the activation of a DNA-binding activity that comigrated with the SCF-induced band, but peaked and was maintained at later time points than SCF-induced activation [29].
  • SCF led to the rapid and transient activation of a DNA-binding factor that was identified by supershift analysis as STAT-5 [29].
  • The MGF complexes formed upon initiation of lactation in the mammary gland and upon stimulation of mammary epithelial cells with PRL migrated at the same position in electrophoretic mobility shift assay, whereas the MGF complex found in mammary gland extracts of pregnant mice exhibited a faster mobility [30].
  • This finding indicates that MGF regulates the DNA binding activity of YY1 and thereby may cause the relief of transcriptional repression [31].

Regulatory relationships of Kitl

  • These findings represent the first demonstration in vivo that a c-kit ligand can result in the functional activation of any cellular lineage expressing the c-kit receptor, and suggest that interactions between the c-kit receptor and its ligand may influence mast cell biology through complex effects on proliferation, maturation, and function [32].
  • Mouse bone marrow-derived mast cells (BMMCs) developed with interleukin 3 (IL-3) can be stimulated by c-kit ligand (KL) and accessory cytokines over a period of hours for direct delayed prostaglandin (PG) generation or over a period of days to prime for augmented IgE-dependent PG and leukotriene (LT) production, as previously reported [33].
  • Thus, the present studies show the potent ability of Tpo to enhance the growth of primitive multipotent murine BM progenitors in combination with multiple early acting cytokines and documents its unique ability to synergize with SCF to enhance Mk production from such progenitors [34].
  • Post-transcriptional stabilization by interleukin-1beta of interleukin-6 mRNA induced by c-kit ligand and interleukin-10 in mouse bone marrow-derived mast cells [35].
  • By using an in vitro oocytes culture system, we found that oocytes-derived Akt and FKHRL1 are regulated by SCF [36].

Other interactions of Kitl

  • We have also provided biological and physical evidence that SCF is a ligand for the c-kit receptor [1].
  • Our results are consistent with the conclusion that SLF, Epo, IL-4, and IL-6 are important during the early stages of ES cell differentiation and hematopoietic development [37].
  • Both Kit+ and KitA+ isoforms showed increased autophosphorylation and enhanced association with phosphatidylinositol (PI) 3' kinase and PLC gamma 1, when stimulated with recombinant soluble Steel factor [38].
  • Furthermore, the combination of SCF with IL-3, but not the other cytokines, exhibited an increase in bone marrow-derived mast cell proliferation [39].
  • We have also found that the mast cells generated in colonies stimulated by IL-4, IL-10, and SCF produced high levels of histamine (6-8 pg per cell) [40].

Analytical, diagnostic and therapeutic context of Kitl

  • Here we report an in situ hybridization analysis comparing the expression profiles of MGF and c-kit transcripts during mouse embryogenesis [41].
  • Flow cytometry showed that, unlike the cells treated with soluble SLF, no downmodulation of cell-surface KIT expression was observed in M07e cells cultured with immobilzed YB5.B8 MoAb [42].
  • Studies using micromanipulation and serum-free culture showed that the effects of sTPOR and SF on the primitive progenitors are direct, not mediated by contaminating stromal cells, and not dependent on factors present in the serum [43].
  • The presence of membrane-bound SF was detected by immunofluorescence, suggesting the possibility that secreted or membrane-bound SF may, at least in part, contribute to the density-dependent growth of AML blasts [5].
  • Moreover, both Sl and W mice responded to the bile duct ligation, similar to the control mice, by developing new bile ducts [44].


  1. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Zsebo, K.M., Williams, D.A., Geissler, E.N., Broudy, V.C., Martin, F.H., Atkins, H.L., Hsu, R.Y., Birkett, N.C., Okino, K.H., Murdock, D.C. Cell (1990) [Pubmed]
  2. Developmental abnormalities in Steel17H mice result from a splicing defect in the steel factor cytoplasmic tail. Brannan, C.I., Bedell, M.A., Resnick, J.L., Eppig, J.J., Handel, M.A., Williams, D.E., Lyman, S.D., Donovan, P.J., Jenkins, N.A., Copeland, N.G. Genes Dev. (1992) [Pubmed]
  3. Stem cell factor stimulates neurogenesis in vitro and in vivo. Jin, K., Mao, X.O., Sun, Y., Xie, L., Greenberg, D.A. J. Clin. Invest. (2002) [Pubmed]
  4. Chemical suppression of a subpopulation of primitive hematopoietic progenitor cells: 1,3-butadiene produces a hematopoietic defect similar to steel or white spotted mutations in mice. Colagiovanni, D.B., Stillman, W.S., Irons, R.D. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  5. Product of the Steel locus can replace leukemic cell interaction. Cáceres-Cortés, J.R., Hoang, T. Cancer Res. (1992) [Pubmed]
  6. Interaction of stem cell factor and its receptor c-kit mediates lodgment and acute expansion of hematopoietic cells in the murine spleen. Broudy, V.C., Lin, N.L., Priestley, G.V., Nocka, K., Wolf, N.S. Blood (1996) [Pubmed]
  7. Transient steel factor dependence by neural crest-derived melanocyte precursors. Morrison-Graham, K., Weston, J.A. Dev. Biol. (1993) [Pubmed]
  8. Expression of hepatocyte growth factor/scatter factor and its receptor, MET, suggests roles in human embryonic organogenesis. Kolatsi-Joannou, M., Moore, R., Winyard, P.J., Woolf, A.S. Pediatr. Res. (1997) [Pubmed]
  9. Altered glycosylation of acetylcholinesterase in APP (SW) Tg2576 transgenic mice occurs prior to amyloid plaque deposition. Fodero, L.R., Sáez-Valero, J., McLean, C.A., Martins, R.N., Beyreuther, K., Masters, C.L., Robertson, T.A., Small, D.H. J. Neurochem. (2002) [Pubmed]
  10. The diverse pathogenic potential of anti-DNA antibodies from various sources to induce experimental systemic lupus erythematosus. Swissa, M., Lerner, A., Sasaki, T., Sela, E., Blank, M., Shoenfeld, Y. Pathobiology (1996) [Pubmed]
  11. NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry. Bassermann, F., von Klitzing, C., Münch, S., Bai, R.Y., Kawaguchi, H., Morris, S.W., Peschel, C., Duyster, J. Cell (2005) [Pubmed]
  12. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. McGill, G.G., Horstmann, M., Widlund, H.R., Du, J., Motyckova, G., Nishimura, E.K., Lin, Y.L., Ramaswamy, S., Avery, W., Ding, H.F., Jordan, S.A., Jackson, I.J., Korsmeyer, S.J., Golub, T.R., Fisher, D.E. Cell (2002) [Pubmed]
  13. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N.R., Crystal, R.G., Besmer, P., Lyden, D., Moore, M.A., Werb, Z., Rafii, S. Cell (2002) [Pubmed]
  14. Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3'-kinase is essential for male fertility. Blume-Jensen, P., Jiang, G., Hyman, R., Lee, K.F., O'Gorman, S., Hunter, T. Nat. Genet. (2000) [Pubmed]
  15. The fourth immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction. Blechman, J.M., Lev, S., Barg, J., Eisenstein, M., Vaks, B., Vogel, Z., Givol, D., Yarden, Y. Cell (1995) [Pubmed]
  16. Evidence that stem cell factor is involved in the rebound thrombocytosis that follows 5-fluorouracil treatment. Hunt, P., Zsebo, K.M., Hokom, M.M., Hornkohl, A., Birkett, N.C., del Castillo, J.C., Martin, F. Blood (1992) [Pubmed]
  17. Pancreatic ascites as a powerful inducer of inflammatory cytokines. The role of known vs unknown factors. Denham, W., Yang, J., Fink, G., Zervos, E.E., Carter, G., Norman, J. Archives of surgery (Chicago, Ill. : 1960) (1997) [Pubmed]
  18. Stem cell factor influences neuro-immune interactions: the response of mast cells to pituitary adenylate cyclase activating polypeptide is altered by stem cell factor. Schmidt-Choudhury, A., Meissner, J., Seebeck, J., Goetzl, E.J., Xia, M., Galli, S.J., Schmidt, W.E., Schaub, J., Wershil, B.K. Regul. Pept. (1999) [Pubmed]
  19. Characterization of c-kit-positive neurons in the dorsal root ganglion of mouse. Hirata, T., Kasugai, T., Morii, E., Hirota, S., Nomura, S., Fujisawa, H., Kitamura, Y. Brain Res. Dev. Brain Res. (1995) [Pubmed]
  20. Comparative study of the endotoxemia and endotoxin tolerance on the production of Th cytokines and macrophage interleukin-6: differential regulation of indomethacin. Chae, B.S. Arch. Pharm. Res. (2002) [Pubmed]
  21. Stem cell factor activates telomerase in mouse mitotic spermatogonia and in primordial germ cells. Dolci, S., Levati, L., Pellegrini, M., Faraoni, I., Graziani, G., Di Carlo, A., Geremia, R. J. Cell. Sci. (2002) [Pubmed]
  22. An allelic series of mutations in the kit ligand gene of mice. I. Identification of point mutations in seven ethylnitrosourea-induced Kitl(Steel) alleles. Rajaraman, S., Davis, W.S., Mahakali-Zama, A., Evans, H.K., Russell, L.B., Bedell, M.A. Genetics (2002) [Pubmed]
  23. A role for kit receptor signaling in Leydig cell steroidogenesis. Rothschild, G., Sottas, C.M., Kissel, H., Agosti, V., Manova, K., Hardy, M.P., Besmer, P. Biol. Reprod. (2003) [Pubmed]
  24. Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Copeland, N.G., Gilbert, D.J., Cho, B.C., Donovan, P.J., Jenkins, N.A., Cosman, D., Anderson, D., Lyman, S.D., Williams, D.E. Cell (1990) [Pubmed]
  25. A specific endoplasmic reticulum export signal drives transport of stem cell factor (Kitl) to the cell surface. Paulhe, F., Imhof, B.A., Wehrle-Haller, B. J. Biol. Chem. (2004) [Pubmed]
  26. Analysis of hypomorphic KitlSl mutants suggests different requirements for KITL in proliferation and migration of mouse primordial germ cells. Mahakali Zama, A., Hudson, F.P., Bedell, M.A. Biol. Reprod. (2005) [Pubmed]
  27. Effects of the steel gene product on mouse primordial germ cells in culture. Godin, I., Deed, R., Cooke, J., Zsebo, K., Dexter, M., Wylie, C.C. Nature (1991) [Pubmed]
  28. Steel factor and c-kit receptor: from mutants to a growth factor system. Morrison-Graham, K., Takahashi, Y. Bioessays (1993) [Pubmed]
  29. Stem cell factor activates STAT-5 DNA binding in IL-3-derived bone marrow mast cells. Ryan, J.J., Huang, H., McReynolds, L.J., Shelburne, C., Hu-Li, J., Huff, T.F., Paul, W.E. Exp. Hematol. (1997) [Pubmed]
  30. Prolactin-dependent activation of a tyrosine phosphorylated DNA binding factor in mouse mammary epithelial cells. Welte, T., Garimorth, K., Philipp, S., Doppler, W. Mol. Endocrinol. (1994) [Pubmed]
  31. The nuclear factor YY1 participates in repression of the beta-casein gene promoter in mammary epithelial cells and is counteracted by mammary gland factor during lactogenic hormone induction. Meier, V.S., Groner, B. Mol. Cell. Biol. (1994) [Pubmed]
  32. The rat c-kit ligand, stem cell factor, induces c-kit receptor-dependent mouse mast cell activation in vivo. Evidence that signaling through the c-kit receptor can induce expression of cellular function. Wershil, B.K., Tsai, M., Geissler, E.N., Zsebo, K.M., Galli, S.J. J. Exp. Med. (1992) [Pubmed]
  33. Interleukin 4 suppresses c-kit ligand-induced expression of cytosolic phospholipase A2 and prostaglandin endoperoxide synthase 2 and their roles in separate pathways of eicosanoid synthesis in mouse bone marrow-derived mast cells. Murakami, M., Penrose, J.F., Urade, Y., Austen, K.F., Arm, J.P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  34. Thrombopoietin, but not erythropoietin, directly stimulates multilineage growth of primitive murine bone marrow progenitor cells in synergy with early acting cytokines: distinct interactions with the ligands for c-kit and FLT3. Ramsfjell, V., Borge, O.J., Veiby, O.P., Cardier, J., Murphy, M.J., Lyman, S.D., Lok, S., Jacobsen, S.E. Blood (1996) [Pubmed]
  35. Post-transcriptional stabilization by interleukin-1beta of interleukin-6 mRNA induced by c-kit ligand and interleukin-10 in mouse bone marrow-derived mast cells. Lu-Kuo, J.M., Austen, K.F., Katz, H.R. J. Biol. Chem. (1996) [Pubmed]
  36. Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development. Reddy, P., Shen, L., Ren, C., Boman, K., Lundin, E., Ottander, U., Lindgren, P., Liu, Y.X., Sun, Q.Y., Liu, K. Dev. Biol. (2005) [Pubmed]
  37. Hematopoietic development of embryonic stem cells in vitro: cytokine and receptor gene expression. Schmitt, R.M., Bruyns, E., Snodgrass, H.R. Genes Dev. (1991) [Pubmed]
  38. Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase. Reith, A.D., Ellis, C., Lyman, S.D., Anderson, D.M., Williams, D.E., Bernstein, A., Pawson, T. EMBO J. (1991) [Pubmed]
  39. The role of stem cell factor (c-kit ligand) and inflammatory cytokines in pulmonary mast cell activation. Lukacs, N.W., Kunkel, S.L., Strieter, R.M., Evanoff, H.L., Kunkel, R.G., Key, M.L., Taub, D.D. Blood (1996) [Pubmed]
  40. Cofactors are essential for stem cell factor-dependent growth and maturation of mast cell progenitors: comparative effects of interleukin-3 (IL-3), IL-4, IL-10, and fibroblasts. Rennick, D., Hunte, B., Holland, G., Thompson-Snipes, L. Blood (1995) [Pubmed]
  41. Embryonic RNA expression patterns of the c-kit receptor and its cognate ligand suggest multiple functional roles in mouse development. Keshet, E., Lyman, S.D., Williams, D.E., Anderson, D.M., Jenkins, N.A., Copeland, N.G., Parada, L.F. EMBO J. (1991) [Pubmed]
  42. Immobilized anti-KIT monoclonal antibody induces ligand-independent dimerization and activation of Steel factor receptor: biologic similarity with membrane-bound form of Steel factor rather than its soluble form. Kurosawa, K., Miyazawa, K., Gotoh, A., Katagiri, T., Nishimaki, J., Ashman, L.K., Toyama, K. Blood (1996) [Pubmed]
  43. Soluble thrombopoietin receptor (Mpl) and granulocyte colony-stimulating factor receptor directly stimulate proliferation of primitive hematopoietic progenitors of mice in synergy with steel factor or the ligand for Flt3/Flk2. Ku, H., Hirayama, F., Kato, T., Miyazaki, H., Aritomi, M., Ota, Y., D'Andrea, A.D., Lyman, S.D., Ogawa, M. Blood (1996) [Pubmed]
  44. Coexpression of flt-3 ligand/flt-3 and SCF/c-kit signal transduction system in bile-duct-ligated SI and W mice. Omori, M., Omori, N., Evarts, R.P., Teramoto, T., Thorgeirsson, S.S. Am. J. Pathol. (1997) [Pubmed]
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