FLT3 mutant dimers bind GRB2

Stable Identifier
Reaction [binding]
Homo sapiens
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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
10482988 SHC and SHIP phosphorylation and interaction in response to activation of the FLT3 receptor

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

Leukemia 1999
19438505 A role of Gab2 association in Flt3 ITD mediated Stat5 phosphorylation and cell survival

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

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

Zhang, S, Mantel, C, Broxmeyer, HE

J. Leukoc. Biol. 1999
Normal reaction
Functional status

Gain of function of p-6Y FLT3 extracellular domain, kinase domain and juxtamembrane domain mutant dimers [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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