title: Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8) by the Janus Kinase JAK3.
abstract: BACKGROUND
  The creatine transporter CreaT (SLC6A8), a Na+,Cl- coupled transporter is expressed in diverse tissues including the brain. Genetic defects of SLC6A8 result in mental retardation with seizures. The present study explored the regulation of CreaT by Janus kinase JAK3, which is expressed in a variety of tissues including the brain and participates in the regulation of cell survival and differentiation of neuronal precursor cells.
  
  
  METHODS
  CreaT was expressed in Xenopus laevis oocytes with or without wild-type JAK3, constitutively active A568V JAK3 and inactive K851A JAK3. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp.
  
  
  RESULTS
  Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes co-expression of JAK3 or A568VJAK3, but not co-expression of K851A JAK3 was followed by a significant decrease of creatine induced current. According to kinetic analysis JAK3 significantly decreased the maximal creatine transport rate. In CreaT and JAK3 expressing oocytes the creatine induced current was significantly increased by JAK3 inhibitor WHI-P154 (22 µM).
  
  
  CONCLUSIONS
  JAK3 is a powerful negative regulator of the creatine transporter CreaT.
authors.affiliation: Department of Physiology I, University of Tx00FC;bingen, Germany.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fezai
authors.forename: Jamshed
authors.initials: J
authors.lastname: Warsi
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D003401:Creatine / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D053616:Janus Kinase 3 / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009865:Oocytes; D011799:Quinazolines / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D026901:Membrane Transport Proteins; D011799:Quinazolines; C113888:WHI P154; C080679:creatine transporter; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D003401:Creatine