Abstract
Endothelin (ET)-1 is a 21-amino-acid peptide that is a potent vasoconstrictor and mitogen. By binding to its G-protein coupled receptor, ET-1 stimulates the proliferation of airway smooth-muscle (ASM) cells, which may be involved in the pathogenesis of asthma. The ETB receptor stimulates activation of the extracellular regulated kinase 2 (ERK2), which is thought to be required for proliferation of ASM cells. Our findings reveal that ET rapidly activates Raf, and that dominant-negative Raf interferes with ET-induced ERK activation in ASM cells. Expression of the amino-terminal Ras-binding domain of Raf inhibited ET-induced ERK activation, suggesting that ET-stimulated Raf activation is a Ras-dependent process. Furthermore, ET-stimulated ERK and Raf activation in ASM cells require calcium influx; chelating extracellular calcium or preventing calcium influx through calcium channels inhibited ET-stimulated, but not phorbol ester-stimulated, ERK and Raf activation. Vichi, P., A. Whelchel, H. Knot, M. Nelson, W. Kolch, and J. Posada. 1999. Endothelin-stimulated ERK activation in airway smooth-muscle cells requires calcium influx and Raf activation. Am. J. Respir. Cell Mol. Biol. 20:99-105.
| Original language | English |
|---|---|
| Pages (from-to) | 99-105 |
| Number of pages | 6 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 20 |
| Issue number | 1 |
| Publication status | Published - 1999 |
Keywords
- Animals
- COS Cells
- metabolism: Ca(2+)-Calmodulin Dependent Protein Kinase
- metabolism: Calcium
- pharmacology: Endothelin-1
- Enzyme Activation
- Mitogen-Activated Protein Kinase 1
- enzymology: Muscle, Smooth
- genetics: Proto-Oncogene Proteins c-raf
- Rats
- Receptor, Endothelin B
- genetics: Receptors, Endothelin
- enzymology: Respiratory System
- Signal Transduction
- Transfection
