FLT3 fusions recruit PIK3R1 through phosphorylated GAB2

Stable Identifier
R-HSA-9703439
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
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FLT3 fusions recruit PIK3R1 through phosphorylated GAB2
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FLT3 fusions signal through the PI3K/AKT pathway as assessed by increased phosphorylation of AKT downstream of activated fusions (Grand et al, 2007; Vu et al, 2009; Troadec et al, 20017; Chonabayashi et al, 2013; reviewed in Kazi and Roonstrand, 2019). Recruitment and activation of PI3K is likely mediated by GRB2-GAB2 as is the case for the wild-type receptor, although this has not been directly demonstrated (Zhang et al, 1999; Zhang et al, 2000; Masson et al, 2009).

Literature References
PubMed ID Title Journal Year
19345670 The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation

Xinh, PT, Vu, HA, Kano, Y, Tokunaga, K, Sato, Y

2009
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
23168613 Direct binding of Grb2 has an important role in the development of myeloproliferative disease induced by ETV6/FLT3

Ishikawa, T, Kawamata, S, Ohno, T, Chonabayashi, K, Hishizawa, M, Uchiyama, T, Nagai, Y, Takaori-Kondo, A

Leukemia 2013
31066629 FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications

Kazi, JU, Rönnstrand, L

Physiol. Rev. 2019
27795560 A novel t(3;13)(q13;q12) translocation fusing FLT3 with GOLGB1: toward myeloid/lymphoid neoplasms with eosinophilia and rearrangement of FLT3?

Petit, B, Dobbelstein, S, Chauzeix, J, Touati, M, Gachard, N, Faumont, N, Bertrand, P, Troadec, E, Trimoreau, F, Bordessoule, D, Bastard, C, Feuillard, J

2017
17764812 A constitutively active SPTBN1-FLT3 fusion in atypical chronic myeloid leukemia is sensitive to tyrosine kinase inhibitors and immunotherapy

Grand, FH, Zhang, L, Russell, NH, Cross, NC, Chase, A, Iqbal, S

2007
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
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
Inferred From
Active Flt3:Grb2:p-Y-Gab2 binds Pik3r1 (Mus musculus)
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  (2020-10-06)
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