ET-1 stimulates ERK signaling pathway through sequential activation of PKC and Src in rat myometrial cells
| Autor: | Christine Desmyter, Philippe Robin, S. Harbon, Denis Leiber, Isaline Boulven |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Transcriptional Activation
MAPK/ERK pathway medicine.medical_specialty Physiology Phosphatidylinositol 3-Kinases GTP-Binding Proteins Internal medicine Extracellular medicine Animals Receptors Platelet-Derived Growth Factor Virulence Factors Bordetella Rats Wistar Cells Cultured Protein Kinase C Protein kinase C Phosphoinositide 3-kinase Endothelin-1 biology Kinase Cell Biology Endothelin 1 Rats Cell biology Enzyme Activation ErbB Receptors src-Family Kinases Endocrinology Pertussis Toxin Type C Phospholipases Myometrium ras Proteins biology.protein Female Mitogen-Activated Protein Kinases Mitogens Signal transduction Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | American Journal of Physiology-Cell Physiology. 283:C251-C260 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00601.2001 |
| Popis: | In this study, we analyzed in rat myometrial cells the signaling pathways involved in the endothelin (ET)-1-induced extracellular signal-regulated kinase (ERK) activation required for the induction of DNA synthesis. We found that inhibition of protein kinase C (PKC) by Ro-31–8220 abolished ERK activation. Inhibition of phospholipase C (PLC) by U-73122 or of phosphoinositide (PI) 3-kinase by wortmannin partially reduced ERK activation. A similar partial inhibition was observed after treatment with pertussis toxin or PKC downregulation by phorbol ester treatment. The effect of wortmannin was additive with that produced by PKC downregulation but not with that due to pertussis toxin. These results suggest that both diacylglycerol-sensitive PKC, activated by PLC products, and diacylglycerol-insensitive PKC, possibly activated by a Gi-PI 3-kinase-dependent process, are involved in ET-1-induced ERK activation. These two pathways were found to be activated mainly through the ETAreceptor subtype. ET-1 and phorbol ester stimulated Src activity in a PKC-dependent manner, both responses being abolished in the presence of Ro-31–8220. Inhibition of Src kinases by PP1 abrogated phorbol ester- and ET-1-induced ERK activation. Finally, ET-1 activated Ras in a PP1- and Ro-31–8220-sensitive manner. Altogether, our results indicate that ET-1 induces ERK activation in rat myometrial cells through the sequential stimulation of PKC, Src, and Ras. |
| Databáze: | OpenAIRE |
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