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).
Blain, SW, Ray, A, Larochelle, S, Fisher, RP, James, MK
Eytan, E, Draetta, GF, Hershko, A, Montagnoli, A, Pagano, M, Carrano, AC, Fiore, F
Keidel, EM, Jäkel, H, Grimmler, M, Mund, T, Cilensek, Z, Hengst, L, Waddell, MB, Wang, Y, Kriwacki, RW, Kullmann, M
Jäkel, H, Duyster, J, Nachbaur, D, Götze, KS, Sill, H, Taschler, M, Hengst, L, Podmirseg, SR, Peschel, I
protein tyrosine kinase activity of Active FLT3 [plasma membrane]
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