Reactome | Active FLT3 phosphorylates CDKN1B

Active FLT3 phosphorylates CDKN1B

Stable Identifier

R-HSA-9699578

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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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). 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 Eytan, E, Draetta, GF, Hershko, A, Montagnoli, A, Pagano, M, Carrano, AC, Fiore, F	Genes Dev	1999
17254966	Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases Keidel, EM, Jäkel, H, Grimmler, M, Mund, T, Cilensek, Z, Hengst, L, Waddell, MB, Wang, Y, Kriwacki, RW, Kullmann, M	Cell	2007
28522571	FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27^Kip1 in acute myeloid leukemia Jäkel, H, Duyster, J, Nachbaur, D, Götze, KS, Sill, H, Taschler, M, Hengst, L, Podmirseg, SR, Peschel, I	Haematologica	2017