FLT3 mutants:GRB2:p-Y-GAB2 binds PTPN11

Stable Identifier
R-HSA-9698008
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
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FLT3 mutants:GRB2:p-Y-GAB2 binds PTPN11
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PTPN11 is involved in signaling downstream of activated FLT3 and may be involved in both the MAPK and STAT5 signaling pathways (Heiss et al, 2006; Zhang et al, 1999a, b; Zhang et al, 2000; Masson et al, 2009; Nabinger et al, 2013; Richine et al, 2016). PTPN11 recruitment is dependent on phosphorylation of FLT3 tyrosine residue Y599 and Y842 and may be mediated by binding to phosphorylated receptor-bound GAB2 (Heiss et al, 2006; Zhang et al, 2000; Kazi et al, 2017). Alternate models suggest that PTPN11 may bind directly to the phosphorylated receptor - these models are not mutually exclusive (reviewed in Kazi and Ronnstrand, 2019).

Literature References
PubMed ID Title Journal Year
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
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
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
10080542 Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells

Mantel, C, Zhang, S, Broxmeyer, HE

J. Leukoc. Biol. 1999
9918857 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

Zhang, S, Broxmeyer, HE

Biochem. Biophys. Res. Commun. 1999
31066629 FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications

Kazi, JU, Rönnstrand, L

Physiol. Rev. 2019
19438505 A role of Gab2 association in Flt3 ITD mediated Stat5 phosphorylation and cell survival

Masson, K, Sun, J, Khan, R, Liu, T, Rönnstrand, L

Br. J. Haematol. 2009
28271164 Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD

Li, T, Kazi, JU, Zhao, H, Sun, J, Su, X, Chougule, RA, Gazi, M, Moharram, SA, Rönnstrand, L, Rupar, K, Marhäll, A

Cell. Mol. Life Sci. 2017
11027663 Flt3 ligand induces tyrosine phosphorylation of gab1 and gab2 and their association with shp-2, grb2, and PI3 kinase

Zhang, S, Broxmeyer, HE

Biochem. Biophys. Res. Commun. 2000
Participants
Input
Output
Participates
as an event of
Normal reaction
Active FLT3:GRB2:p-Y-GAB2 binds PTPN11 (Homo sapiens)
Functional status

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

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID: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)
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