title: Fission yeast mitotic regulator Dsk1 is an SR protein-specific kinase.
abstract: Intricate interplay may exist between pre-mRNA splicing and the cell division cycle, and fission yeast Dsk1 appears to play a role in such a connection. Previous genetic analyses have implicated Dsk1 in the regulation of chromosome segregation at the metaphase/anaphase transition. Yet, its protein sequence suggests that Dsk1 may function as a kinase specific for SR proteins, a family of pre-mRNA splicing factors containing arginine-serine repeats. Using an in vitro system with purified components, we showed that Dsk1 phosphorylated human and yeast SR proteins with high specificity. The Dsk1-phosphorylated SF2/ASF protein was recognized strongly by a monoclonal antibody (mAb104) known to bind the in vivo phosphoepitope shared by SR proteins, indicating that the phosphorylation sites resided in the RS domain. Moreover, the fission yeast U2AF65 homolog, Prp2/Mis11 protein, was phosphorylated more efficiently by Dsk1 than by a human SR protein-specific kinase, SRPK1. Thus, these in vitro results suggest that Dsk1 is a fission yeast SR protein-specific kinase, and Prp2/Mis11 is likely an in vivo target for Dsk1. Together with previous genetic data, the studies support the notion that Dsk1 may play a role in coordinating pre-mRNA splicing and the cell division cycle.
authors.affiliation: Department of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Tang
authors.forename: M
authors.initials: M
authors.lastname: Yanagida
authors.forename: R J
authors.initials: RJ
authors.lastname: Lin
mesh_terms: D002453:Cell Cycle / Q000502:physiology; D053487:DEAD-box RNA Helicases; D005656:Fungal Proteins / Q000378:metabolism / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000201:enzymology; D000068103:Serine-Arginine Splicing Factors; D013379:Substrate Specificity
chemical_list: D005656:Fungal Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000068103:Serine-Arginine Splicing Factors; D011494:Protein Kinases; C403617:Dsk1 protein kinase; C490216:SKY1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C066490:PRP2 protein, S cerevisiae; D053487:DEAD-box RNA Helicases