STAT5 activation downstream of FLT3 ITD mutants

Stable Identifier
R-HSA-9702518
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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STAT5 activation downstream of FLT3 ITD mutants
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STAT5 signaling appears to be preferentially activated downstream of FLT3 ITD mutants relative to the wild-type or FLT3 TKD mutants, although this is subject to some debate (Choudhary et al, 2005; Reindl et al, 2006; Bagrintseva et al, 2005; Grundler et al, 2003; Choudhary et al, 2007; Marhall et al, 2018; reviewed in Choudhary et al, 2005). STAT5 activation contributes to oncogenesis by promoting the transcription of a number of factors involved in regulating cell cycle progression, proliferation and apoptosis, among others (Kim et al, 2005; Nabinger et al, 2013; Takahashi et al, 2004; Godfrey et al, 2012; Hayakawa et al, 2000; reviewed in Murphy and Rani, 2015).
Literature References
PubMed ID Title Journal Year
22438257 Cell transformation by FLT3 ITD in acute myeloid leukemia involves oxidative inactivation of the tumor suppressor protein-tyrosine phosphatase DEP-1/ PTPRJ

Bauer, R, Godfrey, R, Müller, JP, Schnetzke, U, Dagnell, M, Böhmer, SA, Heinrich, T, Böhmer, FD, Arora, D, Stopp, S, Östman, A, Scholl, S

Blood 2012
29372308 Internal tandem duplication mutations in the tyrosine kinase domain of FLT3 display a higher oncogenic potential than the activation loop D835Y mutation

Heidel, F, Rönnstrand, L, Fischer, T, Marhäll, A

2018
15498859 Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival

Levis, M, Ahn, JY, Small, D, Lilly, M, Kim, KT, Meltzer, P, Baird, K

Blood 2005
15718420 FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model

Grundler, R, Duyster, J, Peschel, C, Thiede, C, Miething, C

2005
10698507 Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines

Hayakawa, F, Saito, H, Towatari, M, Tanimoto, M, Naoe, T, Kitamura, T, Kiyoi, H

Oncogene 2000
17356133 Activation mechanisms of STAT5 by oncogenic Flt3-ITD

Berdel, WE, Serve, H, Sargin, B, Ueker, A, Böhmer, FD, Brandts, C, Tickenbrock, L, Choudhary, C, Müller-Tidow, C, Schwäble, J

Blood 2007
23103841 The protein tyrosine phosphatase, Shp2, positively contributes to FLT3-ITD-induced hematopoietic progenitor hyperproliferation and malignant disease in vivo

Boswell, HS, Ramdas, B, Feng, GS, Zeng, L, Kapur, R, He, Y, Liu, Z, Zhang, X, Sandusky, GE, Zhang, ZY, Fukuda, S, Li, XJ, Nabinger, SC, Yu, M, Richine, B, Chan, RJ, Goenka, S, Bowling, JD

Leukemia 2013
15769897 AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations

Berdel, WE, Serve, H, Sargin, B, Kindler, T, Brandts, C, Tickenbrock, L, Choudhary, C, Müller-Tidow, C, Fischer, T, Schwäble, J

2005
15003515 Flt3 mutation activates p21WAF1/CIP1 gene expression through the action of STAT5

Licht, JD, Harigae, H, Takahashi, S, Kaku, M, Sasaki, T

Biochem. Biophys. Res. Commun. 2004
15626738 FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L)

Ellwart, JW, Reindl, C, Spiekermann, K, Geisenhof, S, Kern, R, Bagrintseva, K, Hiddemann, W, Eichenlaub, S

Blood 2005
26716518 STAT5 in Cancer and Immunity

Murphy, JJ, Rani, A

J. Interferon Cytokine Res. 2016
16410449 Point mutations in the juxtamembrane domain of FLT3 define a new class of activating mutations in AML

Schnittger, S, Ellwart, JW, Hopfner, KP, Reindl, C, Spiekermann, K, Wenig, K, Vempati, S, Bagrintseva, K, Hiddemann, W

Blood 2006
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Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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BioModels Database
Authored
Rothfels, K  (2020-11-06)
Reviewed
Kazi, JU  (2020-11-06)
Created
Rothfels, K  (2020-09-30)
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