PDGF upregulates delayed rectifier via Src family kinases and sphingosine kinase in oligodendroglial progenitors.
An increase in the expression of the delayed rectifier current (I(K)) has been shown to correlate with mitogenesis in many cell types. However, pathways involved in the upregulation of I(K) 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 I(K) density and upregulation of Kv1.5 and Kv1.6 mRNA transcripts. The effect of PDGF on I(K) 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 upregulation of Kv1.5 and I(K) density involves Src family tyrosine kinases, sphingosine kinase, and intracellular Ca(2+) but not ERK1/2 or phosphatidylinositol 3-kinase pathways. Furthermore, agents that were effective inhibitors of PDGF-induced I(K) upregulation also attenuated OP proliferation, supporting the concept that I(K) is an important link between PDGF-activated signaling cascades and cell cycle progression.
Soliven
Betty
B
Department of Neurology and Committee on Neurobiology, The Brain Research Institute, University of Chicago, 5841 S. Maryland, Chicago, IL 60637, USA. bsoliven@neurology.bsd.uchicago.edu
Ma
Lan
L
Bae
Hyun
H
Attali
Bernard
B
Sobko
Alexander
A
Iwase
Tamaki
T
D000818:Animals; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051666:Kv1.5 Potassium Channel; D009836:Oligodendroglia / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology* / Q000502:physiology; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D014981:Xenopus; D019061:src-Family Kinases / Q000502:physiology*; D000099157:Sphingosine Kinase
D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D051666:Kv1.5 Potassium Channel; D017853:Phosphotransferases (Alcohol Group Acceptor); D010982:Platelet-Derived Growth Factor; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D019061:src-Family Kinases; D000099157:Sphingosine Kinase; C496983:Kcna5 protein, rat