Active FLT3 phosphorylates CDKN1B

Stable Identifier
R-HSA-9699578
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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).

Literature References
PubMed ID Title Journal Year
10323868 Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation

Montagnoli, A, Fiore, F, Eytan, E, Carrano, AC, Draetta, GF, Hershko, A, Pagano, M

Genes Dev 1999
19075005 p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes

Ray, A, James, MK, Larochelle, S, Fisher, RP, Blain, SW

Mol. Cell. Biol. 2009
17254966 Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases

Grimmler, M, Wang, Y, Mund, T, Cilensek, Z, Keidel, EM, Waddell, MB, Jäkel, H, Kullmann, M, Kriwacki, RW, Hengst, L

Cell 2007
28522571 FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27Kip1 in acute myeloid leukemia

Peschel, I, Podmirseg, SR, Taschler, M, Duyster, J, Götze, KS, Sill, H, Nachbaur, D, Jäkel, H, Hengst, L

Haematologica 2017
Participants
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
protein tyrosine kinase activity of Active FLT3 [plasma membrane]
Physical Entity
Activity
Orthologous Events
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