scholarly journals Extracellular matrix composition determines the transcriptional response to epidermal growth factor receptor activation

2001 ◽  
Vol 98 (8) ◽  
pp. 4472-4477 ◽  
Author(s):  
S. J. Yarwood ◽  
J. R. Woodgett
Keyword(s):  
Extracellular Matrix ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Transcriptional Response ◽  
Receptor Activation ◽  
Matrix Composition ◽  
Epidermal Growth

Neutrophil elastase induces mucin production by ligand-dependent epidermal growth factor receptor activation

2002 ◽  
Vol 283 (3) ◽  
pp. L531-L540 ◽  
Author(s):  
Kazuhiro Kohri ◽  
Iris F. Ueki ◽  
Jay A. Nadel
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Neutrophil Elastase ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Cell Culture Supernatant ◽  
Mucin Production ◽  
Egfr Activation ◽  
Epidermal Growth

Neutrophil products are implicated in hypersecretory airway diseases. To determine the mechanisms linking a proteolytic effect of human neutrophil elastase (HNE) and mucin overproduction, we examined the effects of HNE on MUC5AC mucin production in human airway epithelial (NCI-H292) cells. Stimulation with HNE for 5–30 min induced MUC5AC production 24 h later, which was prevented by HNE serine active site inhibitors, implicating a proteolytic effect of HNE. MUC5AC induction was preceded by epidermal growth factor receptor (EGFR) tyrosine phosphorylation and was prevented by selective EGFR tyrosine kinase inhibitors, implicating EGFR activation. HNE-induced MUC5AC production was inhibited by a neutralizing transforming growth factor-α (TGF-α, an EGFR ligand) antibody and by a neutralizing EGFR antibody but not by oxygen free radical scavengers, further implicating TGF-α and ligand-dependent EGFR activation in the response. HNE decreased pro-TGF-α in NCI-H292 cells and increased TGF-α in cell culture supernatant. From these results, we conclude that HNE-induced MUC5AC mucin production occurs via its proteolytic activation of an EGFR signaling cascade involving TGF-α.

scholarly journals Phosphatidylinositol-4,5-bisphosphate regulates epidermal growth factor receptor activation

2010 ◽  
Vol 461 (3) ◽  
pp. 387-397 ◽  
Author(s):  
Ioannis E. Michailidis ◽  
Radda Rusinova ◽  
Anastasios Georgakopoulos ◽  
Yibang Chen ◽  
Ravi Iyengar ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Epidermal Growth
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