EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKC delta, and sphingosine kinase 1 in glioblastoma cells

Paugh  BS; Paugh  SW; Bryan  LKapitonov  DWilczynska  KMGopalan  SMRokita  HMilstien  SSpiegel  SKordula  T

首页> 外文期刊>The FASEB Journal >EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKC delta, and sphingosine kinase 1 in glioblastoma cells

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EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKC delta, and sphingosine kinase 1 in glioblastoma cells

机译：EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKC delta, and sphingosine kinase 1 in glioblastoma cells

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Patients with gliomas expressing high levels of epidermal growth factor receptor ( EGFR) and plasminogen activator inhibitor-1 (PAI-1) have a shorter overall survival prognosis. Moreover, EGF enhances PAI-1 expression in glioma cells. Although multiple known signaling cascades are activated by EGF in glioma cells, we show for the first time that EGF enhances expression of PAI-1 via sequential activation of c-Src, protein kinase C delta (PKC delta), and sphingosine kinase 1 (SphK1), the enzyme that produces sphingosine-1-phosphate. EGF induced rapid phosphorylation of c-Src and PKC delta and concomitant translocation of PKC delta as well as SphK1 to the plasma membrane. Down-regulation of PKC delta abolished EGF-induced SphK1 translocation and up-regulation of PAI-1 by EGF; whereas, down-regulation of PKC alpha had no effect on the EGF-induced PAI-1 activation but enhanced its basal expression. Similarly, inhibition of c-Src activity by PP2 blocked both EGF-induced translocation of SphK1 and PKC delta to the plasma membrane and up-regulation of PAI-1 expression. Furthermore, SphK1 was indispensable for both EGF-induced c-Jun phosphorylation and PAI-1 expression. Collectively, our results provide a functional link between three critical downstream targets of EGF, c-Src, PKC delta, and SphK1 that have all been implicated in regulating motility and invasion of glioma cells.

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《The FASEB Journal》 |2008年第2期|455-465|共11页
作者
Paugh BS; Paugh SW; Bryan LKapitonov DWilczynska KMGopalan SMRokita HMilstien SSpiegel SKordula T;
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作者单位

Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Dept Biochem & Mol Biol, Richmond, VA 23298 USA;

Jagiellonian Univ, Fac Biotechnol, Krakow, Poland;

NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA;

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原文格式 PDF
正文语种英语
中图分类生物化学;
关键词
glioma; invasiveness; EPIDERMAL-GROWTH-FACTOR; HUMAN-BRAIN-TUMORS; FACTOR RECEPTOR GENE; HUMAN GLIOMA-CELLS; UROKINASE-TYPE; TRANSCRIPTION FACTOR; NECROSIS-FACTOR; BREAST-CANCER; ONCOSTATIN-M; KAPPA-B;

EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c-Src, PKC delta, and sphingosine kinase 1 in glioblastoma cells

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