Dephosphorylation of Cdk2 Thr160 by the Cyclin-Dependent Kinase-Interacting Phosphatase KAP in the Absence of Cyclin

@article{Poon1995DephosphorylationOC,
  title={Dephosphorylation of Cdk2 Thr160 by the Cyclin-Dependent Kinase-Interacting Phosphatase KAP in the Absence of Cyclin},
  author={Randy Y.C. Poon and Tony Hunter},
  journal={Science},
  year={1995},
  volume={270},
  pages={90 - 93}
}
  • R. Poon, T. Hunter
  • Published 6 October 1995
  • Biology, Chemistry, Computer Science
  • Science
The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr160 in Cdk2) by CDK-activating kinase (CAK). Human KAP (also called Cdi1), a CDK-associated phosphatase, was shown to dephosphorylate Thr160 in human Cdk2. KAP was unable to dephosphorylate Tyr15 and only dephosphorylated Thr160 in native monomeric Cdk2. The binding of cyclin A to Cdk2 inhibited the dephosphorylation of Thr160 by KAP but did not preclude the binding of KAP to the cyclin A… 
Binding of HTm4 to Cyclin-dependent Kinase (Cdk)-associated Phosphatase (KAP)·Cdk2·Cyclin A Complex Enhances the Phosphatase Activity of KAP, Dissociates Cyclin A, and Facilitates KAP Dephosphorylation of Cdk2*
TLDR
In vitro data is presented showing the direct interaction between the HTm4 C terminus and KAP Tyr141 that not only facilitates access of KAP to Thr160 and accelerates KAP kinetics, but also forces exclusion of cyclin A from the KAP·cdk2 complex.
Autocatalytic Phosphorylation of CDK2 at the Activating Thr160
TLDR
It is demonstrated that monomeric human CDK2 purified from bacteria is phosphorylated at Thr-160 and that CDK 2 is capable of autophosphorylation at T160, consistent with a role ofCDK2 in auto-activation.
Degradation of Cyclin A Does Not Require Its Phosphorylation by CDC2 and Cyclin-dependent Kinase 2*
TLDR
Evidence is presented that the degradation of human cyclin A can be inhibited by kinase-inactive mutants of CDK2 and CDC2 and surprising, in marked contrast to cyclin E, where phosphorylation of Thr-380 byCDK2 is required for proteolysis, degradation of Cyclin A was not affected by Ser-154 phosphorylated.
Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases.
TLDR
It is shown that type 2C protein phosphatases (PP2Cs) are responsible for this dephosphorylation of Cdc28p, the major budding yeast CDK, and that the substrate specificity of PP2Cs toward CDKs is evolutionarily conserved.
Phosphorylations of Cyclin-dependent Kinase 2 Revisited Using Two-dimensional Gel Electrophoresis*
TLDR
The high resolution power of two-dimensional gel electrophoresis, combined to Tyr-15- or Thr-160-phosphospecific antibodies, is introduced here to re-assess the precise relationship between the different phosphorylations of CDK2, and the influence of cyclins and CDK inhibitors upon them.
REGULATION OF CDK DEPHOSPHORYLATION
TLDR
Data from time-lapse movies suggest that whereas Cdc25A may mainly regulate nuclear events, CDC25B probably regulates events in both the nucleus and the cytoplasm, which is in support of bistability governing Cyclin B1/Cdk1 activation.
Xenopus phospho-CDK7/cyclin H expressed in baculoviral-infected insect cells.
TLDR
Analysis by mass spectrometry showed that coexpression ofCDK7 with cyclin H in baculoviral-infected insect cells results in phosphorylation of residues Ser170 and Thr176 in CDK7, which is assumed thatosphorylation is promoted by kinase(s) in the insect cells that results in the correct, physiologically significant posttranslational modification.
The cdk-activating kinase (CAK): from yeast to mammals
  • P. Kaldis
  • Biology, Computer Science
    Cellular and Molecular Life Sciences CMLS
  • 1999
Abstract Cell cycle progression is regulated by cyclin-dependent kinases (cdks). The activity of cdks is tightly controlled by several mechanisms, including binding of subunits to cdks (cyclins and
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