NDLI: Putting one step before the other: distinct activation pathways for Cdk1 and Cdk2 bring order to the mammalian cell cycle.

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Putting one step before the other: distinct activation pathways for Cdk1 and Cdk2 bring order to the mammalian cell cycle.

Content Provider	Scilit
Author	Merrick, Karl A. Fisher, Robert P.
Copyright Year	2010
Description	Eukaryotic cell division is controlled by the activity of cyclin-dependent kinases (CDKs). Cdk1 and Cdk2, which function at different stages of the mammalian cell cycle, both require cyclin-binding and phosphorylation of the activation (T-) loop for full activity, but differ with respect to the order in which the two steps occur in vivo. To form stable complexes with either of its partners-cyclins A and B-Cdk1 must be phosphorylated on its T-loop, but that phosphorylation in turn depends on the presence of cyclin. Cdk2 can follow a kinetically distinct path to activation in which T-loop phosphorylation precedes cyclin-binding, and thereby out-compete the more abundant Cdk1 for limiting amounts of cyclin A. Mathematical modeling suggests this could be a principal basis for the temporal ordering of CDK activation during S phase, which may dictate the sequence in which replication origins fire. Still to be determined are how: (1) the activation machinery discriminates between closely related CDKs, and (2) coordination of the cell cycle is affected when this mechanism of pathway insulation breaks down.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851199/pdf
Ending Page	714
Page Count	9
Starting Page	706
ISSN	15384101
e-ISSN	15514005
DOI	10.4161/cc.9.4.10732
Journal	Cell Cycle
Issue Number	4
Volume Number	9
Language	English
Publisher	Informa UK Limited
Publisher Date	2010-02-15
Access Restriction	Open
Subject Keyword	Journal: Cell Cycle Biology Phosphorylation Mammalian Cell Cycle Cdk1 and Cdk2 Mathematical Modeling Cyclin Binding Cdks
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine Molecular Biology

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