title: Targeted disruption of the mouse PAS domain serine/threonine kinase PASKIN.
abstract: PASKIN is a novel mammalian serine/threonine kinase containing two PAS (Per-Arnt-Sim) domains. PASKIN is related to the Rhizobium oxygen sensor protein FixL and to AMP-regulated kinases. Like FixL, the sensory PAS domain of PASKIN controls the kinase activity by autophosphorylation in a (unknown) ligand-dependent manner. In Saccharomyces cerevisiae, the two PASKIN orthologues PSK1 and PSK2 phosphorylate three translation factors and two enzymes involved in glycogen synthesis, thereby coordinately regulating protein synthesis and glycolytic flux. To elucidate the function of mammalian PASKIN, we inactivated the mouse Paskin gene by homologous recombination in embryonic stem cells. Paskin(-/-) mice showed normal development, growth, and reproduction. The targeted integration of a lacZ reporter gene allowed the identification of the cell types expressing mouse PASKIN. Surprisingly, PASKIN expression is strongly upregulated in postmeiotic germ cells during spermatogenesis. However, fertility and sperm production and motility were not affected by the PASKIN knockout. The Ppp1r7 gene encoding Sds22, a regulatory subunit of protein phosphatase 1, shares the promoter region with the Paskin gene, pointing towards a common transcriptional regulation. Indeed, Sds22 colocalized with the cell types expressing PASKIN in vivo, suggesting a functional role of protein phosphatase-1 in the regulation of PASKIN autophosphorylation.
authors.affiliation: Cell Physiology Group, Medical Faculty, Martin Luther University Halle, D-06112 Halle, Germany.
authors.forename: Dörthe M
authors.initials: DM
authors.lastname: Katschinski
authors.forename: Hugo H
authors.initials: HH
authors.lastname: Marti
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Wagner
authors.forename: Junpei
authors.initials: J
authors.lastname: Shibata
authors.forename: Katrin
authors.initials: K
authors.lastname: Eckhardt
authors.forename: Falk
authors.initials: F
authors.lastname: Martin
authors.forename: Reinhard
authors.initials: R
authors.lastname: Depping
authors.forename: Uwe
authors.initials: U
authors.lastname: Paasch
authors.forename: Max
authors.initials: M
authors.lastname: Gassmann
authors.forename: Birgit
authors.initials: B
authors.lastname: Ledermann
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desbaillets
authors.forename: Roland H
authors.initials: RH
authors.lastname: Wenger
mesh_terms: D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013081:Sperm Motility; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology; D013737:Testis / Q000378:metabolism
chemical_list: C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1