TY - JOUR
T1 - Down-regulation of WNK1 protein kinase in neural progenitor cells suppresses cell proliferation and migration
AU - Sun, Xutong
AU - Gao, Luoyi
AU - Yu, Robert K.
AU - Zeng, Guichao
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Antisense inhibition
KW - Cell growth
KW - Cell migration
KW - Growth factors
KW - MAP kinase
KW - Neural progenitor cells
UR - http://www.scopus.com/inward/record.url?scp=33750484312&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750484312&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2006.04159.x
DO - 10.1111/j.1471-4159.2006.04159.x
M3 - Article
C2 - 17018027
AN - SCOPUS:33750484312
VL - 99
SP - 1114
EP - 1121
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 4
ER -