title: Presumed pseudokinase VRK3 functions as a BAF kinase.
abstract: Vaccinia-related kinase 3 (VRK3) is known as a pseudokinase that is catalytically inactive due to changes in motifs that are essential for kinase activity. Although VRK3 has been regarded as a genuine pseudokinase from structural and biochemical studies, recent reports suggest that VRK3 acts as an active kinase as well as a signaling scaffold in cells. Here, we demonstrate that VRK3 phosphorylates the nuclear envelope protein barrier-to-autointegration factor (BAF) on Ser4. Interestingly, VRK3 kinase activity is dependent upon its N-terminal regulatory region, which is excluded from the determination of its crystal structure. Furthermore, the kinase activity of VRK3 is involved in the regulation of the cell cycle. VRK3 expression levels increase during interphase, whereas VRK1 is enriched in late G2 and early M phase. Ectopic expression of VRK3 induces the translocation of BAF from the nucleus to the cytoplasm. In addition, depletion of VRK3 decreases the population of proliferating cells. These data suggest that VRK3-mediated phosphorylation of BAF may facilitate DNA replication or gene expression by facilitating the dissociation of nuclear envelope proteins and chromatin during interphase.
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology(POSTECH), Hyoja Dong, San 31, Pohang 790-784, Republic of Korea.
authors.forename: Choon-Ho
authors.initials: CH
authors.lastname: Park
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology(POSTECH), Hyoja Dong, San 31, Pohang 790-784, Republic of Korea.
authors.forename: Hye Guk
authors.initials: HG
authors.lastname: Ryu
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology(POSTECH), Hyoja Dong, San 31, Pohang 790-784, Republic of Korea.
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology(POSTECH), Hyoja Dong, San 31, Pohang 790-784, Republic of Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology(POSTECH), Hyoja Dong, San 31, Pohang 790-784, Republic of Korea.
authors.forename: Haengjin
authors.initials: H
authors.lastname: Song
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology(POSTECH), Hyoja Dong, San 31, Pohang 790-784, Republic of Korea; Department of Life Sciences, Pohang University of Science and Technology(POSTECH), Hyoja Dong, San 31, Pohang 790-784, Republic of Korea. Electronic address: ktk@postech.ac.kr.
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000818:Animals; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D013329:Structure-Activity Relationship
chemical_list: C501959:BANF1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; C583259:VRK3 protein, human; C475142:Vrk3 protein, mouse
keywords: Barrier-to-autointegration factor; Pseudokinase; Vaccinia-related kinase 3