Active FLT3 binds PTPN11

Stable Identifier
R-HSA-9604969
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Feline McDonough Sarcoma-like tyrosine kinase (FLT3) is a member of the class III tyrosine kinase receptor family. Ligand binding induces conformational changes in the FLT3 receptor, which facilitates its dimerization and autophosphorylation. Once fully active, tyrosine-protein phosphatase non-receptor type 11 (PTPN11) has been reported to directly bind to the Y599 site of Flt3 receptors thereby facilitating downstream regulation of effectors (Heiss et al. 2006, Nabinger et al. 2013). Experiments confirming this event were performed in mouse cells. Interaction of FLT3 with PTPN11 is known to trigger STAT5 activation in various pathological conditions (Mizuki M et al. 2000, Rocnik JL et al. 2006).

Literature References
PubMed ID Title Journal Year
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

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

Blood 2006
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
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
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
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