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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.
AuthorsChoon-Ho Park, Hye Guk Ryu, Seong-Hoon Kim, Dohyun Lee, Haengjin Song, Kyong-Tai Kim
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1853 Issue 7 Pg. 1738-48 (Jul 2015) ISSN: 0006-3002 [Print] Netherlands
PMID25899223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • BANF1 protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Phosphoserine
  • Protein-Serine-Threonine Kinases
  • VRK3 protein, human
  • Vrk3 protein, mouse
Topics
  • Animals
  • Cell Cycle
  • DNA-Binding Proteins (metabolism)
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Models, Biological
  • Nuclear Envelope (metabolism)
  • Nuclear Proteins (metabolism)
  • Phosphorylation
  • Phosphoserine (metabolism)
  • Protein Binding
  • Protein Transport
  • Protein-Serine-Threonine Kinases (chemistry, metabolism)
  • Structure-Activity Relationship

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