FLT3 ITD mutants bind STAT5 through GAB2:PTPN11

Stable Identifier
Reaction [binding]
Homo sapiens
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PTPN11 and FLT3 Y599 are required for the recruitment and activation of the STAT5 signaling pathway. STAT5 signaling appears to be more active in FLT3 mutant proteins, particularly FLT3 alleles bearing internal tandem duplications, than it is in wild-type signaling (Hayakawa et al, 2000; Mizuki et al, 2000; Takahashi et al, 2004; Spiekermann et al, 2003; Heiss et al, 2006; Nabinger et al, 2013; Richine et al, 2016; reviewed in Kazi and Ronnstrand, 2019).
Literature References
PubMed ID Title Journal Year
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

Büchner, T, Kratz-Albers, K, Serve, H, Matsumura, I, Müller, C, Serve, S, Steur, C, Kanakura, Y, Berdel, WE, Schmidt, R, Halfter, H, Fenski, R, Grüning, W, Kienast, J, Mizuki, M

Blood 2000
16684964 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

Masson, K, Sun, J, Bengtsson, S, Pedersen, M, Heiss, E, Sundberg, C, Rönnstrand, L

Blood 2006
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
12796379 Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells

Schwab, R, Spiekermann, K, Schmieja, K, Bagrintseva, K, Hiddemann, W

Clin. Cancer Res. 2003
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
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
27256702 Syk kinase and Shp2 phosphatase inhibition cooperate to reduce FLT3-ITD-induced STAT5 activation and proliferation of acute myeloid leukemia

Boswell, HS, Liu, Z, Ramdas, B, Zhang, ZY, Virts, EL, Kapur, R, Naoye, R, Chan, RJ, Mali, R, Bowling, JD, Richine, BM

Leukemia 2016
Normal reaction
Functional status

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

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