Reactome | Active FLT3:GRB2:p-GAB2:PIK3R1 binds PIK3CA

Active FLT3:GRB2:p-GAB2:PIK3R1 binds PIK3CA

Stable Identifier

R-HSA-9698170

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Active FLT3:GRB2:p-GAB2:PIK3R1 binds PIK3CA

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The 110 kDa catalytic subunit of PI3K is recruited to the activated FLT3 receptor through interaction with the p85 regulatory subunit. GAB2-mediated conformational changes in the p85 regulatory subunit stimulate interaction with p110, and promote PI3K/AKT signaling downstream of the activated FLT3 receptor (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