Historical Background
Receptor tyrosine kinases are cell surface receptors that transduce signals mainly from extracellular stimuli leading to activation of numerous intracellular signaling cascades. The human genome encodes 58 receptor tyrosine kinases which can be subdivided into 20 different families (Lemmon and Schlessinger 2010). Within the 20 different families, the type III receptor tyrosine kinase family, also known as PDGFR family, consists of five receptor tyrosine kinases including PDGFRA, PDGFRB, KIT, CSF1R, and FLT3. The Fms-like tyrosine kinase 3 (FLT3) is a receptor for the dimeric FLT3 ligand (FL). The receptor was first described by two different groups in human and mouse (Matthews et al. 1991; Rosnet and Marchetto. 1991; Rosnet et al. 1991). In human, it was mapped to chromosome 13q12 and in mouse it was mapped to chromosome 5.
FLT3 Gene and Protein
The human FLT3 open reading frame (coding sequence) contains 2979 nucleotides and...
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References
Beslu N, LaRose J, Casteran N, Birnbaum D, Lecocq E, Dubreuil P, et al. Phosphatidylinositol-3′ kinase is not required for mitogenesis or internalization of the Flt3/Flk2 receptor tyrosine kinase. J Biol Chem. 1996;271:20075–81.
Birg F, Courcoul M, Rosnet O, Bardin F, Pebusque MJ, Marchetto S, et al. Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the myeloid and lymphoid lineages. Blood. 1992;80:2584–93.
Carow CE, Levenstein M, Kaufmann SH, Chen J, Amin S, Rockwell P, et al. Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood. 1996;87:1089–96.
Heiss E, Masson K, Sundberg C, Pedersen M, Sun J, Bengtsson S, et al. 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;108:1542–50. doi:10.1182/blood-2005-07-008896.
Kazi JU, Rönnstrand L. FLT3 signals via the adapter protein Grb10 and overexpression of Grb10 leads to aberrant cell proliferation in acute myeloid leukemia. Mol Oncol. 2013a;7:402–18. doi:10.1016/j.molonc.2012.11.003.
Kazi JU, Rönnstrand L. Suppressor of cytokine signaling 2 (SOCS2) associates with FLT3 and negatively regulates downstream signaling. Mol Oncol. 2013b;7:693–703. doi:10.1016/j.molonc.2013.02.020.
Kazi JU, Sun J, Phung B, Zadjali F, Flores-Morales A, Rönnstrand L. Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3. J Biol Chem. 2012;287:36509–17. doi:10.1074/jbc.M112.376111.
Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141:1117–34. doi:10.1016/j.cell.2010.06.011.
Mackarehtschian K, Hardin JD, Moore KA, Boast S, Goff SP, Lemischka IR. Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity. 1995;3:147–61.
Masson K, Liu T, Khan R, Sun J, Rönnstrand L. A role of Gab2 association in Flt3 ITD mediated Stat5 phosphorylation and cell survival. Br J Haematol. 2009;146:193–202. doi:10.1111/j.1365-2141.2009.07725.x.
Matthews W, Jordan CT, Wiegand GW, Pardoll D, Lemischka IR. A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. Cell. 1991;65:1143–52. doi:10.1016/0092–8674(91)90010-V.
McClanahan T, Culpepper J, Campbell D, Wagner J, Franz-Bacon K, Mattson J, et al. Biochemical and genetic characterization of multiple splice variants of the Flt3 ligand. Blood. 1996;88:3371–82.
Moharram SA, Chougule RA, Su X, Li T, Sun J, Zhao H, et al. Src-like adaptor protein 2 (SLAP2) binds to and inhibits FLT3 signaling. Oncotarget. 2016; doi:10.18632/oncotarget.10760.
Oshikawa G, Nagao T, Wu N, Kurosu T, Miura O. c-Cbl and Cbl-b ligases mediate 17-allylaminodemethoxygeldanamycin-induced degradation of autophosphorylated Flt3 kinase with internal tandem duplication through the ubiquitin proteasome pathway. J Biol Chem. 2011;286:30263–73. doi:10.1074/jbc.M111.232348.
Puissant A, Fenouille N, Alexe G, Pikman Y, Bassil CF, Mehta S, et al. SYK is a critical regulator of FLT3 in acute myeloid leukemia. Cancer Cell. 2014;25:226–42. doi:10.1016/j.ccr.2014.01.022.
Rosnet O, Marchetto S. deLapeyriere O, Birnbaum D. Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the PDGFR/CSF1R family. Oncogene. 1991;6:1641–50.
Rosnet O, Mattei MG, Marchetto S, Birnbaum D. Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene. Genomics. 1991;9:380–5.
Rosnet O, Buhring HJ, Marchetto S, Rappold I, Lavagna C, Sainty D, et al. Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. Leukemia. 1996;10:238–48.
Zhang S, Broxmeyer HE. p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates with SHP2, SHIP, and a tyrosine-phosphorylated 100-kDa protein in Flt3 ligand-stimulated hematopoietic cells. Biochem Biophys Res Commun. 1999;254:440–5. doi:10.1006/bbrc.1998.9959.
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Kazi, J.U., Moharram, S.A., Rönnstrand, L. (2016). FMS-Like Tyrosine Kinase-3. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101667-1
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DOI: https://doi.org/10.1007/978-1-4614-6438-9_101667-1
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