Abstract
The epithelial lining of the asthmatic airway is exposed to compressive stress as a consequence of smooth muscle constriction. We have shown previously that in vitro compression of bronchial epithelial cells stimulates extracellular signal-regulated kinase (ERK) phosphorylation and downstream gene expression. Here we show that inhibition of signaling through the epidermal growth factor receptor (EGFR) with a tyrosine kinase inhibitor (AG1478) or a neutralizing antibody to the ligand-binding domain of the EGFR blocks compression-induced ERK phosphorylation. A metalloprotease inhibitor (Galardin) and a neutralizing antibody to heparin binding epidermal growth factor (HB-EGF), but not EGF, also attenuates the compression-induced ERK activation. Our results demonstrate that compressive activation of the ERK signaling pathway requires signaling through the EGFR, and involves metalloprotease-dependent shedding of HB-EGF.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 641-642 |
| Number of pages | 2 |
| Journal | Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings |
| Volume | 1 |
| State | Published - Dec 1 2002 |
| Event | Proceedings of the 2002 IEEE Engineering in Medicine and Biology 24th Annual Conference and the 2002 Fall Meeting of the Biomedical Engineering Society (BMES / EMBS) - Houston, TX, United States Duration: Oct 23 2002 → Oct 26 2002 |
Keywords
- EGF receptor
- MAP kinase
- Mechanotransduction
ASJC Scopus subject areas
- Signal Processing
- Biomedical Engineering
- Computer Vision and Pattern Recognition
- Health Informatics