Active FLT3 binds to the cyclin dependent kinase inihibitor CDKN1B (also known as p27 KIP1) and phosphorylates it at tyrosine 88. (Peschel et al, 2017). Phosphorylation at Y88 dislodges the 3-10 helix of CDKN1B from the active site of CDK2 or CDK4, thus paritally relieving CDKN1B-dependent inhibition (Grimmler et al. 2007, Ray et al. 2009). This enables CDK2 (and possibly CDK4) to phosphorylate CDKN1B on threonine residue T187, which is a prerequisite for ubiquitin-mediated degradation of CDKN1B (Montagnoli et al. 1999, Grimmler et al. 2007).
Montagnoli, A, Fiore, F, Eytan, E, Carrano, AC, Draetta, GF, Hershko, A, Pagano, M
Ray, A, James, MK, Larochelle, S, Fisher, RP, Blain, SW
Grimmler, M, Wang, Y, Mund, T, Cilensek, Z, Keidel, EM, Waddell, MB, Jäkel, H, Kullmann, M, Kriwacki, RW, Hengst, L
Peschel, I, Podmirseg, SR, Taschler, M, Duyster, J, Götze, KS, Sill, H, Nachbaur, D, Jäkel, H, Hengst, L
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