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Gene Review

Kit  -  kit oncogene

Mus musculus

Synonyms: Bs, CD117, Dominant white spotting, Fdc, Gsfsco1, ...
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Disease relevance of Kit


Psychiatry related information on Kit


High impact information on Kit

  • Interactions between Gq and Kit receptor tyrosine kinase signaling can mediate coordinate or independent control of skin and hair color [9].
  • Transplantation of spermatogonial stem cells from male Cnot7(-/-) mice to seminiferous tubules of Kit mutant mice (Kit(W/W-v)) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7(-/-) condition [10].
  • To identify Mitf-dependent Kit transcriptional targets in primary melanocytes, microarray studies were undertaken [11].
  • 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 [12].
  • Signalling by the W/Kit receptor tyrosine kinase is negatively regulated in vivo by the protein tyrosine phosphatase Shp1 [13].

Chemical compound and disease context of Kit


Biological context of Kit

  • These data suggest a diversity of normal Kit signalling pathways and indicate that W mutant phenotypes result from primary defects in the Kit receptor that affect its interaction with cytoplasmic signalling proteins [18].
  • Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase [18].
  • In contrast, tyrosine 821 is essential for Kit-mediated mitogenesis and survival, but not cell adhesion [19].
  • These observations demonstrate a role for Steel factor/Kit signaling in the adult nervous system and suggest that a severe deficit in hippocampal-dependent learning need not be associated with reduced hippocampal long-term potentiation [20].
  • In the mouse, mutations in the c-Kit proto-oncogene, a member of the receptor tyrosine kinase (RTK) gene family, have pleiotropic effects on hematopoiesis, pigmentation and fertility (dominant spotting, W) [21].

Anatomical context of Kit

  • We conclude, that association of Kit with p85PI3-K, and thus with PI3-kinase activity, is necessary for a full mitogenic as well as adhesive response in mast cells [19].
  • Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration [22].
  • Stem cell factor (SCF) has crucial roles in proliferation, survival, and differentiation of hematopoietic stem cells and mast cells through binding to c-Kit receptor (KIT) [22].
  • The comparison of the patterns of lacZ-expressing cells between WlacZ/+ and WlacZ/WlacZ embryos allowed us to detect where and when melanoblasts, primordial germ cells and hematopoietic progenitors failed to survive in the absence of Kit [23].
  • Previous studies demonstrated that c-Kit is functionally required for the proliferation of hemopoietic progenitor cells at various differentiation stages in adult bone marrow [24].

Associations of Kit with chemical compounds

  • Based on the role of the sphingomyelin (SM) cycle apoptotic pathway in IR-induced apoptosis, we hypothesized that one of the Kit signaling components might inhibit IR-induced ceramide production or ceramide-induced apoptosis [25].
  • Furthermore, Kit receptors can be down-regulated by proteolytic cleavage induced by either activation of protein kinase C or by isopropyl alcohol [26].
  • Microinjection in mouse eggs of tr-kit, a truncated form of the c-kit tyrosine kinase present in mouse spermatozoa, causes resumption of meiosis through activation of phospholipase Cgamma1 (PLCgamma1) and Ca(2+) mobilization from intracellular stores [27].
  • Mast cells from c-kit mutant mice adhere to fibronectin on stimulation with phorbol 12-myristate 13-acetate (PMA), but not on stimulation with steel factor, indicating that stimulation of integrin adhesiveness requires activation of the c-kit protein tyrosine kinase [28].
  • In addition, the cyclic secretion of luteinizing hormone immediately and dramatically results in elevated Steel expression in mural granulosa cells and decreased levels of c-kit transcripts in stromal-derived cells [29].
  • Our results clearly demonstrate that the c-Kit receptor is involved in the regulation of glucose metabolism, likely through an important role in beta-cell development and function [30].

Physical interactions of Kit

  • 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 [31].

Enzymatic interactions of Kit

  • However, recent studies have shown that there is a physical association between these 2 receptors and that c-kit can phosphorylate EPO-R [32].
  • In contrast, in the transformed mast cell line P815, Kit is constitutively phosphorylated and binds to PI3K in the absence of ligand [33].

Regulatory relationships of Kit

  • 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 [34].
  • Northern blot and flow cytometry analyses showed that mi/mi-CMC expressed much less c-kit at both protein and message levels than +/+-CMC [35].
  • We tested the hypothesis that cell survival in Kit mutant mice would be enhanced by p53 deficiency in vivo [36].
  • Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase [27].
  • Additionally, we present evidence that Kit tyrosine phosphorylation acts as a switch to promote complex formation with PI3K [33].

Other interactions of Kit


Analytical, diagnostic and therapeutic context of Kit


  1. Resistance to friend virus-induced erythroleukemia in W/W(v) mice is caused by a spleen-specific defect which results in a severe reduction in target cells and a lack of Sf-Stk expression. Subramanian, A., Teal, H.E., Correll, P.H., Paulson, R.F. J. Virol. (2005) [Pubmed]
  2. Enhancement of murine blast cell colony formation in culture by recombinant rat stem cell factor, ligand for c-kit. Tsuji, K., Zsebo, K.M., Ogawa, M. Blood (1991) [Pubmed]
  3. c-kit marks late retinal progenitor cells and regulates their differentiation in developing mouse retina. Koso, H., Satoh, S., Watanabe, S. Dev. Biol. (2007) [Pubmed]
  4. W/Wv marrow stromal cells engraft and enhance early erythropoietic progenitors in unconditioned Sl/Sld murine recipients. Bubnic, S.J., Wang, X.H., Clark, B.R., Keating, A. Bone Marrow Transplant. (2002) [Pubmed]
  5. Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1. Piao, X., Paulson, R., van der Geer, P., Pawson, T., Bernstein, A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. Gab2 is involved in differential phosphoinositide 3-kinase signaling by two splice forms of c-Kit. Sun, J., Pedersen, M., Rönnstrand, L. J. Biol. Chem. (2008) [Pubmed]
  7. 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]
  8. The interstitial cells of Cajal and a gastroenteric pacemaker system. Takayama, I., Horiguchi, K., Daigo, Y., Mine, T., Fujino, M.A., Ohno, S. Arch. Histol. Cytol. (2002) [Pubmed]
  9. Effects of G-protein mutations on skin color. Van Raamsdonk, C.D., Fitch, K.R., Fuchs, H., de Angelis, M.H., Barsh, G.S. Nat. Genet. (2004) [Pubmed]
  10. Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta. Nakamura, T., Yao, R., Ogawa, T., Suzuki, T., Ito, C., Tsunekawa, N., Inoue, K., Ajima, R., Miyasaka, T., Yoshida, Y., Ogura, A., Toshimori, K., Noce, T., Yamamoto, T., Noda, T. Nat. Genet. (2004) [Pubmed]
  11. 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]
  12. 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]
  13. Signalling by the W/Kit receptor tyrosine kinase is negatively regulated in vivo by the protein tyrosine phosphatase Shp1. Paulson, R.F., Vesely, S., Siminovitch, K.A., Bernstein, A. Nat. Genet. (1996) [Pubmed]
  14. Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor. Roskoski, R. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  15. Bone marrow norepinephrine mediates development of functionally different macrophages after thermal injury and sepsis. Cohen, M.J., Shankar, R., Stevenson, J., Fernandez, R., Gamelli, R.L., Jones, S.B. Ann. Surg. (2004) [Pubmed]
  16. Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation. Zappulla, J.P., Dubreuil, P., Desbois, S., Létard, S., Hamouda, N.B., Daëron, M., Delsol, G., Arock, M., Liblau, R.S. J. Exp. Med. (2005) [Pubmed]
  17. The multi-targeted kinase inhibitor SU5416 inhibits small cell lung cancer growth and angiogenesis, in part by blocking Kit-mediated VEGF expression. Litz, J., Sakuntala Warshamana-Greene, G., Sulanke, G., Lipson, K.E., Krystal, G.W. Lung Cancer (2004) [Pubmed]
  18. 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]
  19. Differential roles of PI3-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells. Serve, H., Yee, N.S., Stella, G., Sepp-Lorenzino, L., Tan, J.C., Besmer, P. EMBO J. (1995) [Pubmed]
  20. Steel mutant mice are deficient in hippocampal learning but not long-term potentiation. Motro, B., Wojtowicz, J.M., Bernstein, A., van der Kooy, D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  21. Physical mapping of the Tec and Gabrb1 loci reveals that the Wsh mutation on mouse chromosome 5 is associated with an inversion. Nagle, D.L., Kozak, C.A., Mano, H., Chapman, V.M., Bućan, M. Hum. Mol. Genet. (1995) [Pubmed]
  22. Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration. Ueda, S., Mizuki, M., Ikeda, H., Tsujimura, T., Matsumura, I., Nakano, K., Daino, H., Honda Zi, Z., Sonoyama, J., Shibayama, H., Sugahara, H., Machii, T., Kanakura, Y. Blood (2002) [Pubmed]
  23. Spatial and temporal patterns of c-kit-expressing cells in WlacZ/+ and WlacZ/WlacZ mouse embryos. Bernex, F., De Sepulveda, P., Kress, C., Elbaz, C., Delouis, C., Panthier, J.J. Development (1996) [Pubmed]
  24. Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo. Ogawa, M., Nishikawa, S., Yoshinaga, K., Hayashi, S., Kunisada, T., Nakao, J., Kina, T., Sudo, T., Kodama, H., Nishikawa, S. Development (1993) [Pubmed]
  25. Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gamma 1: implication in stem cell factor radioprotective effect. Maddens, S., Charruyer, A., Plo, I., Dubreuil, P., Berger, S., Salles, B., Laurent, G., Jaffrézou, J.P. Blood (2002) [Pubmed]
  26. Mechanism of down-regulation of c-kit receptor. Roles of receptor tyrosine kinase, phosphatidylinositol 3'-kinase, and protein kinase C. Yee, N.S., Hsiau, C.W., Serve, H., Vosseller, K., Besmer, P. J. Biol. Chem. (1994) [Pubmed]
  27. Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase. Sette, C., Paronetto, M.P., Barchi, M., Bevilacqua, A., Geremia, R., Rossi, P. EMBO J. (2002) [Pubmed]
  28. Steel factor and c-kit regulate cell-matrix adhesion. Kinashi, T., Springer, T.A. Blood (1994) [Pubmed]
  29. Dynamic changes in ovarian c-kit and Steel expression during the estrous reproductive cycle. Motro, B., Bernstein, A. Dev. Dyn. (1993) [Pubmed]
  30. c-Kit in early onset of diabetes: a morphological and functional analysis of pancreatic beta-cells in c-KitW-v mutant mice. Krishnamurthy, M., Ayazi, F., Li, J., Lyttle, A.W., Woods, M., Wu, Y., Yee, S.P., Wang, R. Endocrinology (2007) [Pubmed]
  31. Steel factor and c-kit receptor: from mutants to a growth factor system. Morrison-Graham, K., Takahashi, Y. Bioessays (1993) [Pubmed]
  32. Residual erythroid progenitors in W/W mice respond to erythropoietin in the absence of steel factor signals. Pharr, P.N., Hofbauer, A., Worthington, R.E., Longmore, G.D. Int. J. Hematol. (2000) [Pubmed]
  33. The Steel/W transduction pathway: kit autophosphorylation and its association with a unique subset of cytoplasmic signaling proteins is induced by the Steel factor. Rottapel, R., Reedijk, M., Williams, D.E., Lyman, S.D., Anderson, D.M., Pawson, T., Bernstein, A. Mol. Cell. Biol. (1991) [Pubmed]
  34. 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]
  35. Low c-kit expression of cultured mast cells of mi/mi genotype may be involved in their defective responses to fibroblasts that express the ligand for c-kit. Ebi, Y., Kanakura, Y., Jippo-Kanemoto, T., Tsujimura, T., Furitsu, T., Ikeda, H., Adachi, S., Kasugai, T., Nomura, S., Kanayama, Y. Blood (1992) [Pubmed]
  36. Deficiency of Trp53 rescues the male fertility defects of Kit(W-v) mice but has no effect on the survival of melanocytes and mast cells. Jordan, S.A., Speed, R.M., Bernex, F., Jackson, I.J. Dev. Biol. (1999) [Pubmed]
  37. 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]
  38. Structural analysis of chromosomal rearrangements associated with the developmental mutations Ph, W19H, and Rw on mouse chromosome 5. Nagle, D.L., Martin-DeLeon, P., Hough, R.B., Bućan, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  39. Rump white inversion in the mouse disrupts dipeptidyl aminopeptidase-like protein 6 and causes dysregulation of Kit expression. Hough, R.B., Lengeling, A., Bedian, V., Lo, C., Bućan, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  40. 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]
  41. A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Matthews, W., Jordan, C.T., Gavin, M., Jenkins, N.A., Copeland, N.G., Lemischka, I.R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  42. Repression of c-kit and its downstream substrates by GATA-1 inhibits cell proliferation during erythroid maturation. Munugalavadla, V., Dore, L.C., Tan, B.L., Hong, L., Vishnu, M., Weiss, M.J., Kapur, R. Mol. Cell. Biol. (2005) [Pubmed]
  43. Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription factor. Opdecamp, K., Nakayama, A., Nguyen, M.T., Hodgkinson, C.A., Pavan, W.J., Arnheiter, H. Development (1997) [Pubmed]
  44. 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]
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