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

Masanobu Chinami, Yosihiko Yano, Xing Yang, Saira Salahuddin, Kosei Moriyama, Mitsunori Shiroishi, Helen Turner, Taro Shirakawa, Chaker N. Adra

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cyclin-dependent kinase 2 (cdk2) activation requires phosphorylation of Thr160 and dissociation from cyclin A. The T-loop of cdk2 contains a regulatory phosphorylation site at Thr160. An interaction between cdc-associated phosphatase (KAP) and cdk2 compromises the interaction between cdk2 and cyclin A, which permits access of KAP, a Thr160-directed phosphatase, to its substrate, cdk2. We have reported that KAP is bound and activated by a nuclear membrane protein, HTm4. Here, we present in vitro data showing the direct interaction between the HTm4 C terminus and KAP Tyr 141. We show that this interaction not only facilitates access of KAP to Thr160 and accelerates KAP kinetics, but also forces exclusion of cyclin A from the KAP·cdk2 complex.

Original languageEnglish
Pages (from-to)17235-17242
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number17
DOIs
Publication statusPublished - Apr 29 2005

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Cyclin A
Cyclin-Dependent Kinases
Phosphoric Monoester Hydrolases
Cyclin-Dependent Kinase 2
Phosphorylation
Nuclear Envelope
Nuclear Proteins
Membrane Proteins
Chemical activation
Kinetics
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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. / Chinami, Masanobu; Yano, Yosihiko; Yang, Xing; Salahuddin, Saira; Moriyama, Kosei; Shiroishi, Mitsunori; Turner, Helen; Shirakawa, Taro; Adra, Chaker N.

In: Journal of Biological Chemistry, Vol. 280, No. 17, 29.04.2005, p. 17235-17242.

Research output: Contribution to journalArticle

Chinami, Masanobu ; Yano, Yosihiko ; Yang, Xing ; Salahuddin, Saira ; Moriyama, Kosei ; Shiroishi, Mitsunori ; Turner, Helen ; Shirakawa, Taro ; Adra, Chaker N. / 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. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 17. pp. 17235-17242.
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abstract = "Cyclin-dependent kinase 2 (cdk2) activation requires phosphorylation of Thr160 and dissociation from cyclin A. The T-loop of cdk2 contains a regulatory phosphorylation site at Thr160. An interaction between cdc-associated phosphatase (KAP) and cdk2 compromises the interaction between cdk2 and cyclin A, which permits access of KAP, a Thr160-directed phosphatase, to its substrate, cdk2. We have reported that KAP is bound and activated by a nuclear membrane protein, HTm4. Here, we present in vitro data showing the direct interaction between the HTm4 C terminus and KAP Tyr 141. We show that this interaction not only facilitates access of KAP to Thr160 and accelerates KAP kinetics, but also forces exclusion of cyclin A from the KAP·cdk2 complex.",
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T1 - 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

AU - Chinami, Masanobu

AU - Yano, Yosihiko

AU - Yang, Xing

AU - Salahuddin, Saira

AU - Moriyama, Kosei

AU - Shiroishi, Mitsunori

AU - Turner, Helen

AU - Shirakawa, Taro

AU - Adra, Chaker N.

PY - 2005/4/29

Y1 - 2005/4/29

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AB - Cyclin-dependent kinase 2 (cdk2) activation requires phosphorylation of Thr160 and dissociation from cyclin A. The T-loop of cdk2 contains a regulatory phosphorylation site at Thr160. An interaction between cdc-associated phosphatase (KAP) and cdk2 compromises the interaction between cdk2 and cyclin A, which permits access of KAP, a Thr160-directed phosphatase, to its substrate, cdk2. We have reported that KAP is bound and activated by a nuclear membrane protein, HTm4. Here, we present in vitro data showing the direct interaction between the HTm4 C terminus and KAP Tyr 141. We show that this interaction not only facilitates access of KAP to Thr160 and accelerates KAP kinetics, but also forces exclusion of cyclin A from the KAP·cdk2 complex.

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