FLT3 mutants recruit PIK3CA through PIK3R1

Stable Identifier
R-HSA-9698174
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
ReviewStatus
5/5
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FLT3 mutants recruit PIK3CA through PIK3R1
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The 110 kDa catalytic subunit of PI3K is recruited to the mutant FLT3 receptor through interaction with the p85 regulatory subunit, as is the case for the wild-type receptor. GAB2-mediated conformational changes in the p85 regulatory subunit stimulate interaction with p110, and promote PI3K/AKT signaling downstream of activated FLT3 (Zhang et al, 1999; Zhang et al, 2000; Masson et al, 2009; Mandelker et al, 2009; Burke et al, 2011; reviewed in Kazi and Ronnstrand, 2019).
Literature References
PubMed ID Title Journal Year
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
31066629 FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications

Kazi, JU, Rönnstrand, L

Physiol. Rev. 2019
21827948 Dynamics of the phosphoinositide 3-kinase p110? interaction with p85? and membranes reveals aspects of regulation distinct from p110?

Vadas, O, Burke, JE, Finegan, T, Williams, RL, Perisic, O, Berndt, A

Structure 2011
19805105 A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane

Cheong, I, Mandelker, D, Zhu, J, Schmidt-Kittler, O, Kinzler, KW, Vogelstein, B, Amzel, LM, Gabelli, SB, Huang, CH

Proc. Natl. Acad. Sci. U.S.A. 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
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
Participants
Input
Output
Participates
as an event of
Normal reaction
Active FLT3:GRB2:p-GAB2:PIK3R1 binds PIK3CA (Homo sapiens)
Functional status

Gain of function of p-6Y FLT3 mutant dimers:GRB2:p-Y GAB2:PIK3R1 [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  (2020-08-24)
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