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.
Masson, K, Sun, J, Khan, R, Liu, T, Rönnstrand, L
Marchetto, S, Aurran-Schleinitz, T, Fournier, E, Beslu, N, Rosnet, O, Borg, JP, Birnbaum, D, Dubreuil, P
Kazi, JU, Rönnstrand, L
Masson, K, Sun, J, Bengtsson, S, Pedersen, M, Heiss, E, Sundberg, C, Rönnstrand, L
Mantel, C, Zhang, S, Broxmeyer, HE
Gain of function of p-6Y FLT3 extracellular domain, kinase domain and juxtamembrane domain mutant dimers [plasma membrane]
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