TY - JOUR
T1 - PDGF upregulates delayed rectifier via Src family kinases and sphingosine kinase in oligodendroglial progenitors
AU - Soliven, Betty
AU - Ma, Lan
AU - Bae, Hyun
AU - Attali, Bernard
AU - Sobko, Alexander
AU - Iwase, Tamaki
PY - 2003/1/1
Y1 - 2003/1/1
N2 - An increase in the expression of the delayed rectifier current (Iκ) has been shown to correlate with mitogenesis in many cell types. However, pathways involved in the upregulation of Iκ by growth factors in oligodendroglial progenitors (OPs) have not been well-elucidated. In this study, we found that treatment with platelet-derived growth factor (PDGF) and basic fibroblast growth factor but not ciliary neurotrophic factor resulted in increased Iκ density and upregulation of Kv1.5 and Kv1.6 mRNA transcripts. The effect of PDGF on Iκ was blocked by mimosine, a cell cycle inhibitor, and by genistein, a tyrosine kinase inhibitor. Using inhibitors of PDGF-activated pathways, we found that PDGF-induced up-regulation of Kv1.5 and Iκ density involves Src family tyrosine kinases, sphingosine kinase, and intracellular Ca2+ but not ERK1/2 or phosphatidylinositol 3-kinase pathways. Furthermore, agents that were effective inhibitors of PDGF-induced Iκ upregulation also attenuated OP OF proliferation, supporting the concept that Iκ is an important link between PDGF-activated signaling cascades and cell cycle progression.
AB - An increase in the expression of the delayed rectifier current (Iκ) has been shown to correlate with mitogenesis in many cell types. However, pathways involved in the upregulation of Iκ by growth factors in oligodendroglial progenitors (OPs) have not been well-elucidated. In this study, we found that treatment with platelet-derived growth factor (PDGF) and basic fibroblast growth factor but not ciliary neurotrophic factor resulted in increased Iκ density and upregulation of Kv1.5 and Kv1.6 mRNA transcripts. The effect of PDGF on Iκ was blocked by mimosine, a cell cycle inhibitor, and by genistein, a tyrosine kinase inhibitor. Using inhibitors of PDGF-activated pathways, we found that PDGF-induced up-regulation of Kv1.5 and Iκ density involves Src family tyrosine kinases, sphingosine kinase, and intracellular Ca2+ but not ERK1/2 or phosphatidylinositol 3-kinase pathways. Furthermore, agents that were effective inhibitors of PDGF-induced Iκ upregulation also attenuated OP OF proliferation, supporting the concept that Iκ is an important link between PDGF-activated signaling cascades and cell cycle progression.
KW - Glia
KW - Growth factors
KW - Ion channel modulation
KW - Kv subunits
KW - Oligodendrocyte progenitors
UR - http://www.scopus.com/inward/record.url?scp=0037213603&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00145.2002
DO - 10.1152/ajpcell.00145.2002
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AN - SCOPUS:0037213603
SN - 0363-6143
VL - 284
SP - C85-C93
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 1 53-1
ER -