scholarly journals Neuroglian activates Echinoid to antagonize the Drosophila EGF receptor signaling pathway

Development ◽  
2003 ◽  
Vol 130 (10) ◽  
pp. 2051-2059 ◽  
Author(s):  
R. Islam
Keyword(s):  
Signaling Pathway ◽  
Egf Receptor ◽  
Receptor Signaling ◽  
Receptor Signaling Pathway

Activation of the EGF receptor signaling pathway in human airway epithelial cells exposed to metals

1999 ◽  
Vol 277 (5) ◽  
pp. L924-L931 ◽  
Author(s):  
Weidong Wu ◽  
Lee M. Graves ◽  
Ilona Jaspers ◽  
Robert B. Devlin ◽  
William Reed ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Kinase Activity ◽  
Egf Receptor ◽  
Kinase Inhibitor ◽  
Airway Epithelial Cells ◽  
Metal Exposure ◽  
Epithelial Cell Line ◽  
Receptor Signaling ◽  
Receptor Signaling Pathway

We have previously shown that exposure to combustion-derived metals rapidly (within 20 min) activated mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK), in the human bronchial epithelial cell line BEAS. To study the mechanisms responsible for metal-induced activation of ERK, we examined the effect of noncytotoxic exposures to As, Cu, V, or Zn on the kinases upstream of ERK in the epidermal growth factor (EGF) receptor signaling pathway. Western blotting using phospho-specific ERK1/2 antibody demonstrated the selective MEK1/2 inhibitor PD-98059 blocked metal-induced phosphorylation of ERK1/2. Meanwhile, Western blotting using a phospho-specific MEK1/2 antibody showed that these metals induce a rapid phosphorylation of MEK1/2. Kinase activity assays confirmed the activation of MEK1/2 by metal treatment. Immunoprecipitation studies demonstrated that As, Cu, V, or Zn induces EGF receptor phosphorylation. Furthermore, the EGF receptor-specific tyrosine kinase inhibitor (PD-153035) significantly blocked the phosphorylation of MEK1/2 initiated by metals. Interestingly, we observed low levels of Raf-1 activity that were not increased by metal exposure in these cells through kinase activity assay. Finally, transfection assays showed that MEK1/2 inhibition could inhibit trans-activation of Elk1, a transcription factor in the ERK pathway, in BEAS cells exposed to metals. Together, these data demonstrate that As, Cu, V, and Zn can activate the EGF receptor signaling pathway in BEAS cells and suggest that this mechanism may be involved in pulmonary responses to metal inhalation.

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