Vaccinia-related kinase 2 (VRK2) is a serine/threonine kinase that belongs to the casein kinase 1 family. VRK2 has long been known for its relationship with neurodegenerative disorders such as schizophrenia. However, the role of VRK2 and the substrates associated with it are unknown. Dysbindin is known as one of the strong risk factors for schizophrenia. The expression of dysbindin is indeed significantly reduced in schizophrenia patients. Moreover, dysbindin is involved in neurite outgrowth and regulation of NMDA receptor signaling. Here, we first identified dysbindin as a novel interacting protein of VRK2 through immunoprecipitation. We hypothesized that dysbindin is phosphorylated by VRK2 and further that this phosphorylation plays an important role in the function of dysbindin. We show that VRK2 phosphorylates Ser 297 and Ser 299 of dysbindin using in vitro kinase assay. In addition, we found that VRK2-mediated phosphorylation of dysbindin enhanced ubiquitination of dysbindin and consequently resulted in the decrease in its protein stability through western blotting. Over-expression of VRK2 in human neuroblastoma (SH-SY5Y) cells reduced neurite outgrowth induced by retinoic acid. Furthermore, a phosphomimetic mutant of dysbindin alleviated neurite outgrowth and affected surface expression of N-methyl-d-aspartate 2A, a subunit of NMDA receptor in mouse hippocampal neurons. Together, our work reveals the regulation of dysbindin by VRK2, providing the association of these two proteins, which are commonly implicated in schizophrenia. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
Pubmed ID: 30062698 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets RFWD2
View all literature mentionsThis monoclonal targets GST (91G1) Rabbit mAb
View all literature mentionsThis polyclonal targets His-Tag
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Ubiquitin
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Dysbindin antibody [EPR7042(B)]
View all literature mentionsThis monoclonal targets VRK2 (H-5)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionslaboratory mouse with name C57BL/6JBom from MGI.
View all literature mentionsCell line HEK293-A is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SH-SY5Y is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis monoclonal targets Dysbindin antibody [EPR7042(B)]
View all literature mentionsThis monoclonal targets Ubiquitin
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets VRK2 (H-5)
View all literature mentionsCell line SH-SY5Y is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets HA
View all literature mentions