Reactome | CAK phosphorylates CDK1 bound to CCNB1

CAK phosphorylates CDK1 bound to CCNB1

Stable Identifier

R-HSA-170076

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

Synonyms

CAK-mediated phosphorylation of Cyclin B1:Cdc2 complexes

ReviewStatus

5/5

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Full activity of most CDKs is dependent on CAK mediated phosphorylation at a conserved residue (Thr161 in CDK1, also known as Cdc2). This modification is thought to improve substrate binding. Cyclin B:Cdc2 complexes have considerably low activity in the absence of CAK mediated phosphorylation (Desai et al 1995). CAK is unable to phosphorylate monomeric CDK1 and only phosphorylates it when it is bound to cyclin A or cyclin B (Merrick et al. 2008). Using two-dimensional gel electrophoresis of protein extracts of cycling human cells, it was shown that in CCNB1:CDK1 complexes, the activating T161 phosphorylation never occurs without T14 phosphorylation, indicating that inhibitory phosphorylation of CDK1 at T14 by PKMYT1 precedes the activating phosphorylation at T161 by the CAK complex, thus preventing premature CCNB1:CDK1 activation (Coulonval et al. 2011).

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
7799941	Effects of phosphorylation by CAK on cyclin binding by CDC2 and CDK2. Desai, D, Wessling, HC, Fisher, RP, Morgan, DO	Mol Cell Biol	1995
19061641	Distinct activation pathways confer cyclin-binding specificity on Cdk1 and Cdk2 in human cells Merrick, KA, Larochelle, S, Zhang, C, Allen, JJ, Shokat, KM, Fisher, RP	Mol Cell	2008