Reactome | WEE1 phosphorylates CCNA:CDK1

WEE1 phosphorylates CCNA:CDK1

Stable Identifier

R-HSA-170156

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

Synonyms

Wee1-mediated phosphorylation of Cyclin A:phospho-Cdc2 complexes

ReviewStatus

5/5

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WEE1-mediated tyrosine phosphorylation of CDK1 (Cdc2) bound to either CCNA or CCNB was initially discovered using human CDK1, clam cyclin A or cyclin B, and wee1 from Schizosaccharomyces pombe (Parker et al., 1991). The human WEE1 kinase was subsequently shown to phosphorylates CDK1 on tyrosine 15 (Y15), resulting in inactivation of the CCNB1:CDK1 complex (Watanabe et al., 1995). Two-dimensional gel electrophoresis of protein extracts of cycling human cells has shown that CDK1 triple phosphorylated at T14, Y15, and T161 is the most abundant form of CDK1 that co-immunoprecipitates with CCNA2 or CCNB1, and Y15 phosphorylation of CDK1 was confirmed to be WEE1-dependent (Coulonval et al. 2011). WEE1 inhibition in G2 by a tyrosine kinase inhibitor MK-1775 decreases Y15 phosphorylation on CCNA2-bound CDK1 and CDK2 and promotes the activity of CCNA2:CDK complexes (Gheghiani et al. 2017).

Literature References

PubMed ID	Title	Journal	Year
21900495	Coupling of T161 and T14 phosphorylations protects cyclin B-CDK1 from premature activation Coulonval, K, Kooken, H, Roger, PP	Mol Biol Cell	2011
28591578	PLK1 Activation in Late G2 Sets Up Commitment to Mitosis Gheghiani, L, Loew, D, Lombard, B, Mansfeld, J, Gavet, O	Cell Rep	2017