title: DAP-like kinase interacts with the rat homolog of Schizosaccharomyces pombe CDC5 protein, a factor involved in pre-mRNA splicing and required for G2/M phase transition.
abstract: DAP-like kinase (Dlk, also termed ZIP kinase) is a leucine zipper-containing serine/threonine-specific protein kinase with as yet unknown biological function(s). Interaction partners so far identified are either transcription factors or proteins that can support or counteract apoptosis. Thus, Dlk might be involved in regulating transcription or, more generally, survival or apoptosis. Here we report on a new interaction partner, the rat homolog of Schizosaccharomyces pombe CDC5 protein, a presumptive transcription and splicing factor involved in the G(2)/M transition. In vitro, rat CDC5 forms complexes with, but is not phosphorylated by, Dlk. Rather, it was phosphorylated by an associated kinase which was identified as CK2. The interaction domain of Dlk was mapped to the leucine zipper, while that of CDC5 was mapped to the C-terminal region between residues 500 and 802. In vivo, both proteins co-localize perfectly in distinct speckle-like structures in the nucleus, some of which overlap with promyelocytic leukemia protein. Interestingly, splicing factor SC35, which also resides in speckles, was partially displaced upon overexpression of either CDC5 or Dlk, perhaps due to phosphorylation by Dlk. Together with previous data, these results suggest that Dlk might play a role in coordinating specific transcription and splicing events.
authors.affiliation: Institute of Genetics, University of Bonn, Roemerstrasse 164, D-53117 Bonn, Germany.
authors.forename: Harry
authors.initials: H
authors.lastname: Engemann
authors.forename: Volker
authors.initials: V
authors.lastname: Heinzel
authors.forename: Grit
authors.initials: G
authors.lastname: Page
authors.forename: Ute
authors.initials: U
authors.lastname: Preuss
authors.forename: Karl Heinz
authors.initials: KH
authors.lastname: Scheidtmann
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D064550:Death-Associated Protein Kinases; D016195:G2 Phase; D020930:MAP Kinase Kinase Kinases; D008856:Microscopy, Fluorescence; D008938:Mitosis; D009363:Neoplasm Proteins / Q000032:analysis; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012322:RNA Precursors / Q000378:metabolism; D012326:RNA Splicing; D051381:Rats; D012261:Ribonucleoproteins; D029702:Schizosaccharomyces pombe Proteins / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis; D014162:Transfection; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D012322:RNA Precursors; D012261:Ribonucleoproteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C085875:cdc5 protein, S pombe; D064550:Death-Associated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12