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.
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 Tyr141. 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.
Chinami
Masanobu
M
Department of Nutrition, Kyushu Women's University, Jiyugaoka 1-1, Kitakyushushi 807-8586, Japan.
Yano
Yoshihiko
Y
Yang
Xing
X
Salahuddin
Saira
S
Moriyama
Kosei
K
Shiroishi
Mitsunori
M
Turner
Helen
H
Shirakawa
Taro
T
Adra
Chaker N
CN
D000595:Amino Acid Sequence; D001665:Binding Sites; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002942:Circular Dichroism; D003001:Cloning, Molecular; D019925:Cyclin A / Q000737:chemistry / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004305:Dose-Response Relationship, Drug; D054637:Dual-Specificity Phosphatases; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007477:Ions; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013912:Threonine / Q000737:chemistry; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry
D018797:Cell Cycle Proteins; D019925:Cyclin A; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D007477:Ions; C089821:MS4A3 protein, human; D008565:Membrane Proteins; D011994:Recombinant Proteins; D013912:Threonine; D014443:Tyrosine; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C084429:CDKN3 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases