FLT3 fusion proteins may signal through the PI3K/AKT and MAP kinase signaling pathway by first recruiting GRB2 to the phosphorylated receptor. This has been directly demonstrated for one of the ETV6-FLT3 fusions, where GRB2 binding was shown to depend on tyrosine residues corresponding to Y314 and Y354 of the ETV6 portion and Y768, Y955 and Y969 of the FLT3 portion. Mutation of these residues to phenylalanies abrogates GRB2 binding and interferes with downstream signaling and the ability of the fusion protein to transform BaF3 cells to IL-3-independent growth (Chonabayashi et al, 2013).
Ishikawa, T, Kawamata, S, Ohno, T, Chonabayashi, K, Hishizawa, M, Uchiyama, T, Nagai, Y, Takaori-Kondo, A
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