title: Protein kinase WNK3 regulates the neuronal splicing factor Fox-1.
abstract: We report an action of the protein kinase WNK3 on the neuronal mRNA splicing factor Fox-1. Fox-1 splices mRNAs encoding proteins important in synaptic transmission and membrane excitation. WNK3, implicated in the control of neuronal excitability through actions on ion transport, binds Fox-1 and inhibits its splicing activity in a kinase activity-dependent manner. Phosphorylation of Fox-1 by WNK3 does not change its RNA binding capacity; instead, WNK3 increases the cytoplasmic localization of Fox-1, thereby suppressing Fox-1-dependent splicing. These findings demonstrate a role of WNK3 in RNA processing. Considering the implication of WNK3 and Fox-1 in disorders of neuronal development such as autism, WNK3 may offer a target for treatment of Fox-1-induced disease.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: A-Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Steve
authors.initials: S
authors.lastname: Stippec
authors.forename: Jon
authors.initials: J
authors.lastname: Self
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ding
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Juang
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D003903:Deuterium; D024202:Electrophoretic Mobility Shift Assay; D015723:Gene Library; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D010761:Phosphorus Radioisotopes; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques
chemical_list: D017931:DNA Primers; D010761:Phosphorus Radioisotopes; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C465036:Rbfox1 protein, mouse; D003903:Deuterium; D017346:Protein Serine-Threonine Kinases; C507511:Wnk3 protein, mouse