Receptor-type tyrosine-protein kinase FLT3

Details

Name
Receptor-type tyrosine-protein kinase FLT3
Synonyms
  • 2.7.10.1
  • CD135
  • Fetal liver kinase-2
  • FL cytokine receptor
  • FLK-2
  • FLK2
  • FLT-3
  • Fms-like tyrosine kinase 3
  • Stem cell tyrosine kinase 1
  • STK-1
  • STK1
Gene Name
FLT3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036960|Receptor-type tyrosine-protein kinase FLT3
MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESP
EDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFDL
QNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMENQD
ALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNELGRE
CTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGNYFEM
STYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNSSEDYE
IDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPGEYIFHA
ENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPNCTEEITE
GVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSPGPFPFIQD
NISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFYVDFREYEYD
LKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKADSSEREALMS
ELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREKFHRTWTEIFKE
HNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEYENQKRLEEEEDL
NVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKICDFGLARDIMSDS
NYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGVNPYPGIPVDANFYK
LIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGCQLADAEEAMYQNVDG
RVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS
Number of residues
993
Molecular Weight
112902.51
Theoretical pI
5.5
GO Classification
Functions
ATP binding / cytokine receptor activity / protein homodimerization activity / transmembrane receptor protein tyrosine kinase activity / vascular endothelial growth factor-activated receptor activity
Processes
B cell differentiation / cellular response to cytokine stimulus / common myeloid progenitor cell proliferation / cytokine-mediated signaling pathway / dendritic cell differentiation / hemopoiesis / leukocyte homeostasis / lymphocyte proliferation / myeloid progenitor cell differentiation / negative regulation of B cell differentiation / negative regulation of cell proliferation / peptidyl-tyrosine phosphorylation / positive regulation of cell proliferation / positive regulation of MAP kinase activity / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase activity / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of tyrosine phosphorylation of STAT protein / pro-B cell differentiation / pro-T cell differentiation / protein autophosphorylation / regulation of apoptotic process / transmembrane receptor protein tyrosine kinase signaling pathway / vascular endothelial growth factor signaling pathway
Components
endoplasmic reticulum lumen / external side of plasma membrane / integral component of plasma membrane
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.
Pfam Domain Function
Transmembrane Regions
544-563
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0018920|Receptor-type tyrosine-protein kinase FLT3 (FLT3)
ATGCCGGCGTTGGCGCGCGACGGCGGCCAGCTGCCGCTGCTCGTTGTTTTTTCTGCAATG
ATATTTGGGACTATTACAAATCAAGATCTGCCTGTGATCAAGTGTGTTTTAATCAATCAT
AAGAACAATGATTCATCAGTGGGGAAGTCATCATCATATCCCATGGTATCAGAATCCCCG
GAAGACCTCGGGTGTGCGTTGAGACCCCAGAGCTCAGGGACAGTGTACGAAGCTGCCGCT
GTGGAAGTGGATGTATCTGCTTCCATCACACTGCAAGTGCTGGTCGACGCCCCAGGGAAC
ATTTCCTGTCTCTGGGTCTTTAAGCACAGCTCCCTGAATTGCCAGCCACATTTTGATTTA
CAAAACAGAGGAGTTGTTTCCATGGTCATTTTGAAAATGACAGAAACCCAAGCTGGAGAA
TACCTACTTTTTATTCAGAGTGAAGCTACCAATTACACAATATTGTTTACAGTGAGTATA
AGAAATACCCTGCTTTACACATTAAGAAGACCTTACTTTAGAAAAATGGAAAACCAGGAC
GCCCTGGTCTGCATATCTGAGAGCGTTCCAGAGCCGATCGTGGAATGGGTGCTTTGCGAT
TCACAGGGGGAAAGCTGTAAAGAAGAAAGTCCAGCTGTTGTTAAAAAGGAGGAAAAAGTG
CTTCATGAATTATTTGGGACGGACATAAGGTGCTGTGCCAGAAATGAACTGGGCAGGGAA
TGCACCAGGCTGTTCACAATAGATCTAAATCAAACTCCTCAGACCACATTGCCACAATTA
TTTCTTAAAGTAGGGGAACCCTTATGGATAAGGTGCAAAGCTGTTCATGTGAACCATGGA
TTCGGGCTCACCTGGGAATTAGAAAACAAAGCACTCGAGGAGGGCAACTACTTTGAGATG
AGTACCTATTCAACAAACAGAACTATGATACGGATTCTGTTTGCTTTTGTATCATCAGTG
GCAAGAAACGACACCGGATACTACACTTGTTCCTCTTCAAAGCATCCCAGTCAATCAGCT
TTGGTTACCATCGTAGAAAAGGGATTTATAAATGCTACCAATTCAAGTGAAGATTATGAA
ATTGACCAATATGAAGAGTTTTGTTTTTCTGTCAGGTTTAAAGCCTACCCACAAATCAGA
TGTACGTGGACCTTCTCTCGAAAATCATTTCCTTGTGAGCAAAAGGGTCTTGATAACGGA
TACAGCATATCCAAGTTTTGCAATCATAAGCACCAGCCAGGAGAATATATATTCCATGCA
GAAAATGATGATGCCCAATTTACCAAAATGTTCACGCTGAATATAAGAAGGAAACCTCAA
GTGCTCGCAGAAGCATCGGCAAGTCAGGCGTCCTGTTTCTCGGATGGATACCCATTACCA
TCTTGGACCTGGAAGAAGTGTTCAGACAAGTCTCCCAACTGCACAGAAGAGATCACAGAA
GGAGTCTGGAATAGAAAGGCTAACAGAAAAGTGTTTGGACAGTGGGTGTCGAGCAGTACT
CTAAACATGAGTGAAGCCATAAAAGGGTTCCTGGTCAAGTGCTGTGCATACAATTCCCTT
GGCACATCTTGTGAGACGATCCTTTTAAACTCTCCAGGCCCCTTCCCTTTCATCCAAGAC
AACATCTCATTCTATGCAACAATTGGTGTTTGTCTCCTCTTCATTGTCGTTTTAACCCTG
CTAATTTGTCACAAGTACAAAAAGCAATTTAGGTATGAAAGCCAGCTACAGATGGTACAG
GTGACCGGCTCCTCAGATAATGAGTACTTCTACGTTGATTTCAGAGAATATGAATATGAT
CTCAAATGGGAGTTTCCAAGAGAAAATTTAGAGTTTGGGAAGGTACTAGGATCAGGTGCT
TTTGGAAAAGTGATGAACGCAACAGCTTATGGAATTAGCAAAACAGGAGTCTCAATCCAG
GTTGCCGTCAAAATGCTGAAAGAAAAAGCAGACAGCTCTGAAAGAGAGGCACTCATGTCA
GAACTCAAGATGATGACCCAGCTGGGAAGCCACGAGAATATTGTGAACCTGCTGGGGGCG
TGCACACTGTCAGGACCAATTTACTTGATTTTTGAATACTGTTGCTATGGTGATCTTCTC
AACTATCTAAGAAGTAAAAGAGAAAAATTTCACAGGACTTGGACAGAGATTTTCAAGGAA
CACAATTTCAGTTTTTACCCCACTTTCCAATCACATCCAAATTCCAGCATGCCTGGTTCA
AGAGAAGTTCAGATACACCCGGACTCGGATCAAATCTCAGGGCTTCATGGGAATTCATTT
CACTCTGAAGATGAAATTGAATATGAAAACCAAAAAAGGCTGGAAGAAGAGGAGGACTTG
AATGTGCTTACATTTGAAGATCTTCTTTGCTTTGCATATCAAGTTGCCAAAGGAATGGAA
TTTCTGGAATTTAAGTCGTGTGTTCACAGAGACCTGGCCGCCAGGAACGTGCTTGTCACC
CACGGGAAAGTGGTGAAGATATGTGACTTTGGATTGGCTCGAGATATCATGAGTGATTCC
AACTATGTTGTCAGGGGCAATGCCCGTCTGCCTGTAAAATGGATGGCCCCCGAAAGCCTG
TTTGAAGGCATCTACACCATTAAGAGTGATGTCTGGTCATATGGAATATTACTGTGGGAA
ATCTTCTCACTTGGTGTGAATCCTTACCCTGGCATTCCGGTTGATGCTAACTTCTACAAA
CTGATTCAAAATGGATTTAAAATGGATCAGCCATTTTATGCTACAGAAGAAATATACATT
ATAATGCAATCCTGCTGGGCTTTTGACTCAAGGAAACGGCCATCCTTCCCTAATTTGACT
TCGTTTTTAGGATGTCAGCTGGCAGATGCAGAAGAAGCGATGTATCAGAATGTGGATGGC
CGTGTTTCGGAATGTCCTCACACCTACCAAAACAGGCGACCTTTCAGCAGAGAGATGGAT
TTGGGGCTACTCTCTCCGCAGGCTCAGGTCGAAGATTCGTAG
Chromosome Location
13
Locus
13q12
External Identifiers
ResourceLink
UniProtKB IDP36888
UniProtKB Entry NameFLT3_HUMAN
GenBank Protein ID409573
GenBank Gene IDU02687
GenAtlas IDFLT3
HGNC IDHGNC:3765
General References
  1. Small D, Levenstein M, Kim E, Carow C, Amin S, Rockwell P, Witte L, Burrow C, Ratajczak MZ, Gewirtz AM, et al.: STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):459-63. [PubMed:7507245]
  2. Rosnet O, Schiff C, Pebusque MJ, Marchetto S, Tonnelle C, Toiron Y, Birg F, Birnbaum D: Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells. Blood. 1993 Aug 15;82(4):1110-9. [PubMed:8394751]
  3. Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT: The DNA sequence and analysis of human chromosome 13. Nature. 2004 Apr 1;428(6982):522-8. [PubMed:15057823]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. Rosnet O, Mattei MG, Marchetto S, Birnbaum D: Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene. Genomics. 1991 Feb;9(2):380-5. [PubMed:2004790]
  6. Rosnet O, Buhring HJ, Marchetto S, Rappold I, Lavagna C, Sainty D, Arnoulet C, Chabannon C, Kanz L, Hannum C, Birnbaum D: Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. Leukemia. 1996 Feb;10(2):238-48. [PubMed:8637232]
  7. Nakao M, Yokota S, Iwai T, Kaneko H, Horiike S, Kashima K, Sonoda Y, Fujimoto T, Misawa S: Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996 Dec;10(12):1911-8. [PubMed:8946930]
  8. Kiyoi H, Towatari M, Yokota S, Hamaguchi M, Ohno R, Saito H, Naoe T: Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia. 1998 Sep;12(9):1333-7. [PubMed:9737679]
  9. Zhang S, Mantel C, Broxmeyer HE: Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells. J Leukoc Biol. 1999 Mar;65(3):372-80. [PubMed:10080542]
  10. Mizuki M, Fenski R, Halfter H, Matsumura I, Schmidt R, Muller C, Gruning W, Kratz-Albers K, Serve S, Steur C, Buchner T, Kienast J, Kanakura Y, Berdel WE, Serve H: Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood. 2000 Dec 1;96(12):3907-14. [PubMed:11090077]
  11. Brandts CH, Sargin B, Rode M, Biermann C, Lindtner B, Schwable J, Buerger H, Muller-Tidow C, Choudhary C, McMahon M, Berdel WE, Serve H: Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation. Cancer Res. 2005 Nov 1;65(21):9643-50. [PubMed:16266983]
  12. Schmidt-Arras DE, Bohmer A, Markova B, Choudhary C, Serve H, Bohmer FD: Tyrosine phosphorylation regulates maturation of receptor tyrosine kinases. Mol Cell Biol. 2005 May;25(9):3690-703. [PubMed:15831474]
  13. Rocnik JL, Okabe R, Yu JC, Lee BH, Giese N, Schenkein DP, Gilliland DG: Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD. Blood. 2006 Aug 15;108(4):1339-45. Epub 2006 Apr 20. [PubMed:16627759]
  14. Heiss E, Masson K, Sundberg C, Pedersen M, Sun J, Bengtsson S, Ronnstrand L: Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2. Blood. 2006 Sep 1;108(5):1542-50. Epub 2006 May 9. [PubMed:16684964]
  15. Meshinchi S, Stirewalt DL, Alonzo TA, Boggon TJ, Gerbing RB, Rocnik JL, Lange BJ, Gilliland DG, Radich JP: Structural and numerical variation of FLT3/ITD in pediatric AML. Blood. 2008 May 15;111(10):4930-3. doi: 10.1182/blood-2008-01-117770. Epub 2008 Feb 27. [PubMed:18305215]
  16. Kikushige Y, Yoshimoto G, Miyamoto T, Iino T, Mori Y, Iwasaki H, Niiro H, Takenaka K, Nagafuji K, Harada M, Ishikawa F, Akashi K: Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. J Immunol. 2008 Jun 1;180(11):7358-67. [PubMed:18490735]
  17. Razumovskaya E, Masson K, Khan R, Bengtsson S, Ronnstrand L: Oncogenic Flt3 receptors display different specificity and kinetics of autophosphorylation. Exp Hematol. 2009 Aug;37(8):979-89. doi: 10.1016/j.exphem.2009.05.008. Epub 2009 May 27. [PubMed:19477218]
  18. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195]
  19. Voisset E, Lopez S, Chaix A, Georges C, Hanssens K, Prebet T, Dubreuil P, De Sepulveda P: FES kinases are required for oncogenic FLT3 signaling. Leukemia. 2010 Apr;24(4):721-8. doi: 10.1038/leu.2009.301. Epub 2010 Jan 28. [PubMed:20111072]
  20. Buchwald M, Pietschmann K, Muller JP, Bohmer FD, Heinzel T, Kramer OH: Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for proteasomal degradation. Leukemia. 2010 Aug;24(8):1412-21. doi: 10.1038/leu.2010.114. Epub 2010 May 27. [PubMed:20508617]
  21. Chen W, Drakos E, Grammatikakis I, Schlette EJ, Li J, Leventaki V, Staikou-Drakopoulou E, Patsouris E, Panayiotidis P, Medeiros LJ, Rassidakis GZ: mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3-mutated acute myeloid leukemia cells. Mol Cancer. 2010 Nov 10;9:292. doi: 10.1186/1476-4598-9-292. [PubMed:21067588]
  22. Arora D, Stopp S, Bohmer SA, Schons J, Godfrey R, Masson K, Razumovskaya E, Ronnstrand L, Tanzer S, Bauer R, Bohmer FD, Muller JP: Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3 signaling. J Biol Chem. 2011 Apr 1;286(13):10918-29. doi: 10.1074/jbc.M110.205021. Epub 2011 Jan 24. [PubMed:21262971]
  23. Zheng R, Bailey E, Nguyen B, Yang X, Piloto O, Levis M, Small D: Further activation of FLT3 mutants by FLT3 ligand. Oncogene. 2011 Sep 22;30(38):4004-14. doi: 10.1038/onc.2011.110. Epub 2011 Apr 25. [PubMed:21516120]
  24. Stirewalt DL, Radich JP: The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer. 2003 Sep;3(9):650-65. [PubMed:12951584]
  25. Meshinchi S, Appelbaum FR: Structural and functional alterations of FLT3 in acute myeloid leukemia. Clin Cancer Res. 2009 Jul 1;15(13):4263-9. doi: 10.1158/1078-0432.CCR-08-1123. Epub 2009 Jun 23. [PubMed:19549778]
  26. Griffith J, Black J, Faerman C, Swenson L, Wynn M, Lu F, Lippke J, Saxena K: The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell. 2004 Jan 30;13(2):169-78. [PubMed:14759363]
  27. Verstraete K, Vandriessche G, Januar M, Elegheert J, Shkumatov AV, Desfosses A, Van Craenenbroeck K, Svergun DI, Gutsche I, Vergauwen B, Savvides SN: Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex. Blood. 2011 Jul 7;118(1):60-8. doi: 10.1182/blood-2011-01-329532. Epub 2011 Mar 9. [PubMed:21389326]
  28. Abu-Duhier FM, Goodeve AC, Wilson GA, Care RS, Peake IR, Reilly JT: Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. Br J Haematol. 2001 Jun;113(4):983-8. [PubMed:11442493]
  29. Yamamoto Y, Kiyoi H, Nakano Y, Suzuki R, Kodera Y, Miyawaki S, Asou N, Kuriyama K, Yagasaki F, Shimazaki C, Akiyama H, Saito K, Nishimura M, Motoji T, Shinagawa K, Takeshita A, Saito H, Ueda R, Ohno R, Naoe T: Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001 Apr 15;97(8):2434-9. [PubMed:11290608]
  30. Taketani T, Taki T, Sugita K, Furuichi Y, Ishii E, Hanada R, Tsuchida M, Sugita K, Ida K, Hayashi Y: FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy. Blood. 2004 Feb 1;103(3):1085-8. Epub 2003 Sep 22. [PubMed:14504097]
  31. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846]
  32. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485. [PubMed:18987736]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00398Sorafenibapproved, investigationalyesantagonistDetails
DB01268Sunitinibapproved, investigationalyesinhibitorDetails
DB12874QuizartinibinvestigationalunknownDetails
DB12742AmuvatinibinvestigationalunknownDetails
DB05014XL999investigationalunknownDetails
DB05465TandutinibinvestigationalunknownDetails
DB06080ABT-869investigationalunknownDetails
DB06469LestaurtinibinvestigationalunknownDetails
DB06595Midostaurinapproved, investigationalyesantagonistinhibitorDetails
DB08901Ponatinibapproved, investigationalunknowninhibitorDetails
DB09079NintedanibapprovedunknowninhibitorDetails
DB12267Brigatinibapproved, investigationalunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB12141Gilteritinibapproved, investigationalyesinhibitorDetails