[1] Chan, P.M., Ilangumaran, S., La Rose, J., Chakrabartty, A., and Rottapel, R. (2003). Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region. Mol Cell Biol 23, 3067–3078 .12697809
[2] Choudhary, C., Brandts, C., Schwable, J., Tickenbrock, L., Sargin, B., Ueker, A., B?hmer, F.D., Berdel, W.E., Müller-Tidow, C., and Serve, H. (2007). Activation mechanisms of STAT5 by oncogenic Flt3-ITD. Blood 110, 370–374 .17356133
[3] Choudhary, C., Olsen, J.V., Brandts, C., Cox, J., Reddy, P.N., B?hmer, F.D., Gerke, V., Schmidt-Arras, D.E., Berdel, W.E., Müller-Tidow, C., (2009). Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 36, 326–339 .19854140
[4] Choudhary, C., Schw?ble, J., Brandts, C., Tickenbrock, L., Sargin, B., Kindler, T., Fischer, T., Berdel, W.E., Müller-Tidow, C., and Serve, H. (2005). AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations. Blood 106, 265–273 .15769897
[5] Dosil, M., Wang, S., and Lemischka, I.R. (1993). Mitogenic signalling and substrate specificity of the Flk2/Flt3 receptor tyrosine kinase in fibroblasts and interleukin 3-dependent hematopoietic cells. Mol Cell Biol 13, 6572–6585 .7692230
[6] Gilliland, D.G., and Griffin, J.D. (2002). The roles of FLT3 in hematopoiesis and leukemia. Blood 100, 1532–1542 .12176867
[7] Griffith, J., Black, J., Faerman, C., Swenson, L., Wynn, M., Lu, F., Lippke, J., and Saxena, K. (2004). The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell 13, 169–178 .14759363
[8] Grundler, R., Miething, C., Thiede, C., Peschel, C., and Duyster, J. (2005). FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model. Blood 105, 4792–4799 .15718420
[9] Hayakawa, F., Towatari, M., Kiyoi, H., Tanimoto, M., Kitamura, T., Saito, H., and Naoe, T. (2000). Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 19, 624–631 .10698507
[10] Heiss, E., Masson, K., Sundberg, C., Pedersen, M., Sun, J., Bengtsson, S., and R?nnstrand, L. (2006). 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 108, 1542–1550 .16684964
[11] Huntly, B.J., and Gilliland, D.G. (2005). Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 5, 311–321 .15803157
[12] Kindler, T., Lipka, D.B., and Fischer, T. (2010). FLT3 as a therapeutic target in AML: still challenging after all these years. Blood 116, 5089–5102 .20705759
[13] Kiyoi, H., Naoe, T., Nakano, Y., Yokota, S., Minami, S., Miyawaki, S., Asou, N., Kuriyama, K., Jinnai, I., Shimazaki, C., (1999). Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 93, 3074–3080 .10216104
[14] Kiyoi, H., Ohno, R., Ueda, R., Saito, H., and Naoe, T. (2002). Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain. Oncogene 21, 2555–2563 .11971190
[15] Koch, S., Jacobi, A., Ryser, M., Ehninger, G., and Thiede, C. (2008). Abnormal localization and accumulation of FLT3-ITD, a mutant receptor tyrosine kinase involved in leukemogenesis. Cells Tissues Organs 188, 225–235 .18303245
[16] Kottaridis, P.D., Gale, R.E., Frew, M.E., Harrison, G., Langabeer, S.E., Belton, A.A., Walker, H., Wheatley, K., Bowen, D.T., Burnett, A.K., (2001). The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 98, 1752–1759 .11535508
[17] Levis, M., and Small, D. (2003). FLT3: ITDoes matter in leukemia. Leukemia 17, 1738–1752 .12970773
[18] Lu, Y., Kitaura, J., Oki, T., Komeno, Y., Ozaki, K., Kiyono, M., Kumagai, H., Nakajima, H., Nosaka, T., Aburatani, H., (2007). Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD. Leukemia 21, 2246–2257 .17690703
[19] Mackarehtschian, K., Hardin, J.D., Moore, K.A., Boast, S., Goff, S.P., and Lemischka, I.R. (1995). Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity 3, 147–161 .7621074
[20] Masson, K., Heiss, E., Band, H., and R?nnstrand, L. (2006). Direct binding of Cbl to Tyr568 and Tyr936 of the stem cell factor receptor/c-Kit is required for ligand-induced ubiquitination, internalization and degradation. Biochem J 399, 59–67 .16780420
[21] Masson, K., and R?nnstrand, L. (2009). Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3. Cell Signal 21, 1717–1726 .19540337
[22] Matthews, W., Jordan, C.T., Wiegand, G.W., Pardoll, D., and Lemischka, I.R. (1991). A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations. Cell 65, 1143–1152 .1648448
[23] Mayer, B.J., Hirai, H., and Sakai, R. (1995). Evidence that SH2 domains promote processive phosphorylation by protein-tyrosine kinases. Curr Biol 5, 296–305 .7780740
[24] Meshinchi, S., Alonzo, T.A., Stirewalt, D.L., Zwaan, M., Zimmerman, M., Reinhardt, D., Kaspers, G.J., Heerema, N.A., Gerbing, R., Lange, B.J., (2006). Clinical implications of FLT3 mutations in pediatric AML. Blood 108, 3654–3661 .16912228
[25] Meshinchi, S., and Appelbaum, F.R. (2009). Structural and functional alterations of FLT3 in acute myeloid leukemia. Clin Cancer Res 15, 4263–4269 .19549778
[26] Mol, C.D., Dougan, D.R., Schneider, T.R., Skene, R.J., Kraus, M.L., Scheibe, D.N., Snell, G.P., Zou, H., Sang, B.C., and Wilson, K.P. (2004). Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem 279, 31655–31663 .15123710
[27] Mol, C.D., Lim, K.B., Sridhar, V., Zou, H., Chien, E.Y., Sang, B.C., Nowakowski, J., Kassel, D.B., Cronin, C.N., and McRee, D.E. (2003). Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem 278, 31461–31464 .12824176
[28] Murata, K., Kumagai, H., Kawashima, T., Tamitsu, K., Irie, M., Nakajima, H., Suzu, S., Shibuya, M., Kamihira, S., Nosaka, T., (2003). Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in leukemia cells expressing a constitutively active Fms-like tyrosine kinase 3 (FLT3). J Biol Chem 278, 32892–32898 .12815052
[29] Nakao, M., Yokota, S., Iwai, T., Kaneko, H., Horiike, S., Kashima, K., Sonoda, Y., Fujimoto, T., and Misawa, S. (1996). Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 10, 1911–1918 .8946930
[30] Ong, S.E., Blagoev, B., Kratchmarova, I., Kristensen, D.B., Steen, H., Pandey, A., and Mann, M. (2002). Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1, 376–386 .12118079
[31] Pratz, K.W., Cortes, J., Roboz, G.J., Rao, N., Arowojolu, O., Stine, A., Shiotsu, Y., Shudo, A., Akinaga, S., Small, D., (2009). A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood 113, 3938–3946 .19029442
[32] Razumovskaya, E., Masson, K., Khan, R., Bengtsson, S., and R?nnstrand, L. (2009). Oncogenic Flt3 receptors display different specificity and kinetics of autophosphorylation. Exp Hematol 37, 979–989 .19477218
[33] Rocnik, J.L., Okabe, R., Yu, J.C., Lee, B.H., Giese, N., Schenkein, D.P., and Gilliland, D.G. (2006). Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD. Blood 108, 1339–1345 .16627759
[34] Sargin, B., Choudhary, C., Crosetto, N., Schmidt, M.H., Grundler, R., Rensinghoff, M., Thiessen, C., Tickenbrock, L., Schw?ble, J., Brandts, C., (2007). Flt3-dependent transformation by inactivating c-Cbl mutations in AML. Blood 110, 1004–1012 .17446348
[35] Schmidt-Arras, D., B?hmer, S.A., Koch, S., Müller, J.P., Blei, L., Cornils, H., Bauer, R., Korasikha, S., Thiede, C., and B?hmer, F.D. (2009). Anchoring of FLT3 in the endoplasmic reticulum alters signaling quality. Blood 113, 3568–3576 .19204327
[36] Small, D., Levenstein, M., Kim, E., Carow, C., Amin, S., Rockwell, P., Witte, L., Burrow, C., Ratajczak, M.Z., Gewirtz, A.M., (1994). 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 91, 459–463 .7507245
[37] Stirewalt, D.L., Kopecky, K.J., Meshinchi, S., Engel, J.H., Pogosova-Agadjanyan, E.L., Linsley, J., Slovak, M.L., Willman, C.L., and Radich, J.P. (2006). Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood 107, 3724–3726 .16368883
[38] Stirewalt, D.L., and Radich, J.P. (2003). The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 3, 650–665 .12951584
[39] Tickenbrock, L., Schw?ble, J., Wiedehage, M., Steffen, B., Sargin, B., Choudhary, C., Brandts, C., Berdel, W.E., Müller-Tidow, C., and Serve, H. (2005). Flt3 tandem duplication mutations cooperate with Wnt signaling in leukemic signal transduction. Blood 105, 3699–3706 .15650056
[40] Till, J.H., Chan, P.M., and Miller, W.T. (1999). Engineering the substrate specificity of the Abl tyrosine kinase. J Biol Chem 274, 4995–5003 .9988744
[41] Vempati, S., Reindl, C., Wolf, U., Kern, R., Petropoulos, K., Naidu, V.M., Buske, C., Hiddemann, W., Kohl, T.M., and Spiekermann, K. (2008). Transformation by oncogenic mutants and ligand-dependent activation of FLT3 wild-type requires the tyrosine residues 589 and 591. Clin Cancer Res 14, 4437–4445 .18628457
[42] Walter, M., Lucet, I.S., Patel, O., Broughton, S.E., Bamert, R., Williams, N.K., Fantino, E., Wilks, A.F., and Rossjohn, J. (2007). The 2.7 A crystal structure of the autoinhibited human c-Fms kinase domain. J Mol Biol 367, 839–847 .17292918
[43] Yamamoto, Y., Kiyoi, H., Nakano, Y., Suzuki, R., Kodera, Y., Miyawaki, S., Asou, N., Kuriyama, K., Yagasaki, F., Shimazaki, C., (2001). Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 97, 2434–2439 .11290608
[44] Zhang, S., and Broxmeyer, H.E. (1999). 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 254, 440–445 .9918857
[45] Zhu, H., Pan, S., Gu, S., Bradbury, E.M., and Chen, X. (2002). Amino acid residue specific stable isotope labeling for quantitative proteomics. Rapid Commun Mass Spectrom 16, 2115–2123 .12415544
