FLT3 mutant dimers bind GRB2

Stable Identifier
R-HSA-9695841
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
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FLT3 mutant dimers bind GRB2
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FLT3 mutants signal to the RAS ERK, the PI3K and the STAT pathways through recruitment of GRB2, as is the case for the wild type receptor (Zhang et al, 1999; reviewed in Kazi and Ronnstrand, 2019). Binding to GRB2 depends on phosphorylation of tyrosine residues 768, 955 and 969 (Masson et al, 2009). GRB2 may also be recruited indirectly by binding to receptor-bound PTPN11 or SHC, and some studies show that PTPN11 is required for activation of ERK signaling (Zhang et al, 1999; Marchetto et al, 1999; Heiss et al, 2006; reviewed in Kazi and Ronnstrand, 2019). These alternate mechanisms are not shown in this pathway.

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

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

Blood 2006
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
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
10482988 SHC and SHIP phosphorylation and interaction in response to activation of the FLT3 receptor

Marchetto, S, Aurran-Schleinitz, T, Fournier, E, Beslu, N, Rosnet, O, Borg, JP, Birnbaum, D, Dubreuil, P

Leukemia 1999
Participants
Input
Output
Participates
as an event of
Normal reaction
Active FLT3 dimer binds GRB2 (Homo sapiens)
Functional status

Gain of function of p-6Y FLT3 extracellular domain, kinase domain and juxtamembrane domain mutant dimers [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  (2020-07-15)
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