How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A.

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Citation

Welburn JP, Tucker JA, Johnson T, Lindert L, Morgan M, Willis A, Noble ME, Endicott JA

How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A.

J Biol Chem. 2007 Feb 2;282(5):3173-81. Epub 2006 Nov 9.

PubMed ID
17095507 [ View in PubMed
]
Abstract

Inhibition of cyclin-dependent kinase 1 (CDK1) activity by Tyr-15 phosphorylation directly regulates entry into mitosis and is an important element in the control of the unperturbed cell cycle. Active site phosphorylation of other members of the CDK family that regulate cell cycle progression instates checkpoints that are fundamental to eukaryotic cell cycle regulation. Kinetic and crystallographic analyses of CDK2-cyclin A complexes reveal that this inhibitory mechanism operates through steric blockade of peptide substrate binding and through the creation of an environment that favors a non-productive conformation of the terminal group of ATP. By contrast, tyrosine phosphorylation of CDK2 alters neither its Km for ATP nor its significant intrinsic ATPase activity. Tyr-15-phosphorylated CDK2 retains trace protein phosphorylation activity that should be considered in quantitative and qualitative cell cycle models.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Cyclin-dependent kinase 2P24941Details