title: Down-regulation of WNK1 protein kinase in neural progenitor cells suppresses cell proliferation and migration.
abstract: WNK1, a Ser/Thr protein kinase, is widely expressed in many tissues. Its biological functions are largely unknown. Disruption of the WNK1 gene in mice leads to embryonic lethality at day 13, implicating a critical role of WNK1 in embryonic development. To investigate this potential function, we used antisense strategy to knock down the expression of WNK1 in a mouse neural progenitor cell line, C17.2. Down-regulation of WNK1 in C17.2 cells greatly reduced cell growth. Addition of epidermal growth factor (EGF), a mitogen for C17.2 cells, had no effect on growth. The WNK1-knockdown cells showed a flat and rounded morphology, characteristic of the immature and non-differentiated phenotype of the progenitor cells; this was further demonstrated by immunostaining for the progenitor and neuronal markers. Migration of the WNK1-knockdown C17.2 cells was reduced as tested in culture dishes or Matrigel-covered chambers. Moreover, activation of extracellular signal-regulated kinase (ERK1)/2 and ERK5 by EGF in the WNK1-knockdown cells was suppressed. These results demonstrate a novel function of WNK1 in proliferation, migration, and differentiation of neural progenitor cells, likely by mechanisms involving activation of the mitogen-activated protein (MAP) kinase ERK1/2 and/or ERK5 pathways.
authors.affiliation: Developmental Neurobiology Program, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA. gzeng@mail.mcg.edu
authors.forename: Xutong
authors.initials: X
authors.lastname: Sun
authors.forename: Luoyi
authors.initials: L
authors.lastname: Gao
authors.forename: Robert K
authors.initials: RK
authors.lastname: Yu
authors.forename: Guichao
authors.initials: G
authors.lastname: Zeng
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects / Q000235:genetics; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D000076204:WNK Lysine-Deficient Protein Kinase 1
chemical_list: D015415:Biomarkers; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498744:Wnk1 protein, mouse