Reactome | FLT3 ITD mutants phosphorylate STAT5

FLT3 ITD mutants phosphorylate STAT5

Stable Identifier

R-HSA-9698005

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

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STAT5 is phosphorylated downstream of FLT3 ITD mutants (Hayakawa et al, 2000; Mizuki et al, 2000; Spiekermann et al, 2003, Rocnik et al, 2006). Recombinant FLT3 ITD is able to directly phosphorylate STAT5 in vitro, but phosphorylation may also be mediated by SRC family kinases in vivo (Choudhary et al, 2007; Leischner et al, 2012; Voisset et al, 2010; reviewed in Kazi and Ronnstrand, 2019 a, b). FLT3-dependent STAT5 activation contributes to the expression of a number of genes involved in proliferation and transformation (Mizuki et al 2003; Takahashi et al, 2004; Kim et al, 2005; Nabinger et al, 2013; Bertoli et al, 2015; reviewed in Kazi and Ronnstrand, 2019 a).

Literature References

PubMed ID	Title	Journal	Year
30552988	The role of SRC family kinases in FLT3 signaling Kazi, JU, Rönnstrand, L	Int. J. Biochem. Cell Biol.	2019
20111072	FES kinases are required for oncogenic FLT3 signaling Voisset, E, Lopez, S, Chaix, A, Georges, C, Hanssens, K, Prébet, T, Dubreuil, P, De Sepulveda, P	Leukemia	2010
31066629	FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications Kazi, JU, Rönnstrand, L	Physiol. Rev.	2019
11090077	Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways Mizuki, M, Fenski, R, Halfter, H, Matsumura, I, Schmidt, R, Müller, C, Grüning, W, Kratz-Albers, K, Serve, S, Steur, C, Büchner, T, Kienast, J, Kanakura, Y, Berdel, WE, Serve, H	Blood	2000
17356133	Activation mechanisms of STAT5 by oncogenic Flt3-ITD Choudhary, C, Brandts, C, Schwäble, J, Tickenbrock, L, Sargin, B, Ueker, A, Böhmer, FD, Berdel, WE, Müller-Tidow, C, Serve, H	Blood	2007
10698507	Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines Hayakawa, F, Towatari, M, Kiyoi, H, Tanimoto, M, Kitamura, T, Saito, H, Naoe, T	Oncogene	2000
23103841	The protein tyrosine phosphatase, Shp2, positively contributes to FLT3-ITD-induced hematopoietic progenitor hyperproliferation and malignant disease in vivo Nabinger, SC, Li, XJ, Ramdas, B, He, Y, Zhang, X, Zeng, L, Richine, B, Bowling, JD, Fukuda, S, Goenka, S, Liu, Z, Feng, GS, Yu, M, Sandusky, GE, Boswell, HS, Zhang, ZY, Kapur, R, Chan, RJ	Leukemia	2013
26515730	CDC25A governs proliferation and differentiation of FLT3-ITD acute myeloid leukemia Bertoli, S, Boutzen, H, David, L, Larrue, C, Vergez, F, Fernandez-Vidal, A, Yuan, L, Hospital, MA, Tamburini, J, Demur, C, Delabesse, E, Saland, E, Sarry, JE, Galcera, MO, Mansat-De Mas, V, Didier, C, Dozier, C, Récher, C, Manenti, S	Oncotarget	2015
15498859	Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival Kim, KT, Baird, K, Ahn, JY, Meltzer, P, Lilly, M, Levis, M, Small, D	Blood	2005
12468433	Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations Mizuki, M, Schwäble, J, Steur, C, Choudhary, C, Agrawal, S, Sargin, B, Steffen, B, Matsumura, I, Kanakura, Y, Böhmer, FD, Müller-Tidow, C, Berdel, WE, Serve, H	Blood	2003
12796379	Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells Spiekermann, K, Bagrintseva, K, Schwab, R, Schmieja, K, Hiddemann, W	Clin. Cancer Res.	2003
15003515	Flt3 mutation activates p21WAF1/CIP1 gene expression through the action of STAT5 Takahashi, S, Harigae, H, Kaku, M, Sasaki, T, Licht, JD	Biochem. Biophys. Res. Commun.	2004
22411868	SRC is a signaling mediator in FLT3-ITD- but not in FLT3-TKD-positive AML Leischner, H, Albers, C, Grundler, R, Razumovskaya, E, Spiekermann, K, Bohlander, S, Rönnstrand, L, Götze, K, Peschel, C, Duyster, J	Blood	2012
16627759	Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD Rocnik, JL, Okabe, R, Yu, JC, Lee, BH, Giese, N, Schenkein, DP, Gilliland, DG	Blood	2006

Participants

Input

Output

Participant Of

hasEvent

STAT5 activation downstream of FLT3 ITD mutants

Catalyst Activity

Title

protein tyrosine kinase activity of p-6Y FLT3 ITD mutant dimers:GRB2:p-Y GAB2:PTPN11:STAT5 [plasma membrane]

Physical Entity

p-6Y FLT3 ITD mutant dimers:GRB2:p-Y GAB2:PTPN11:STAT5 [plasma membrane]

Activity

protein tyrosine kinase activity (0004713)

Normal reaction

Activator phosphorylates STAT5 (Homo sapiens)

Disease

Name	Identifier	Synonyms
cancer	162	malignant tumor, malignant neoplasm, primary cancer

Authored

Rothfels, K (2020-11-06)

Reviewed

Kazi, JU (2020-11-06)

Created

Rothfels, K (2020-08-21)