title: The WNK/SPAK and IRBIT/PP1 pathways in epithelial fluid and electrolyte transport.
abstract: Fluid and electrolyte homeostasis is a fundamental physiological function required for survival and is associated with a plethora of diseases when aberrant. Systemic fluid and electrolyte composition is regulated by the kidney, and all secretory epithelia generate biological fluids with defined electrolyte composition by vectorial transport of ions and the obligatory water. A major regulatory pathway that immerged in the last several years is regulation of ion transporters by the WNK/SPAK kinases and IRBIT/PP1 pathways. The IRBIT/PP1 pathway functions to reverse the effects of the WNK/SPAK kinases pathway, as was demonstrated for NBCe1-B and CFTR. Since many transporters involved in fluid and electrolyte homeostasis are affected by PP1 and/or calcineurin, it is possible that WNK/SPAK and IRBIT/PP1 form a common regulatory pathway to tune the activity of fluid and electrolyte transport in response to physiological demands.
authors.affiliation: Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, Maryland, USA.
authors.forename: Seonghee
authors.initials: S
authors.lastname: Park
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Hong
authors.forename: Ehud
authors.initials: E
authors.lastname: Ohana
authors.forename: Shmuel
authors.initials: S
authors.lastname: Muallem
mesh_terms: D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D017136:Ion Transport / Q000502:physiology*; D037181:Lectins, C-Type / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D015778:Minor Histocompatibility Antigens; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000076204:WNK Lysine-Deficient Protein Kinase 1; D014882:Water-Electrolyte Balance / Q000502:physiology
chemical_list: C470184:CLECL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D017476:Receptors, Neuropeptide Y; C109491:neuropeptide Y4 receptor; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human