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Figure 2 | Particle and Fibre Toxicology

Figure 2

From: Diesel exhaust increases EGFR and phosphorylated C-terminal Tyr 1173 in the bronchial epithelium

Figure 2

Description of possible involved signalling pathways. Schematically description of possible involved signalling pathways in the activation and phosphorylation of EGFR, protein tyrosine kinases and downstream signalling following DE exposure. Extended and modified from Puddicombe SM et al. Clinical and Experimental Allergy, 2000, 30, 7–11. The graph is inserted to allow for better understanding of the pathways and mediators discussed in this paper and is by no means conclusive. The yellow box shows the PTK activation pathway through cellular and oxidative stress, cytokine receptors and GPCR. N-SH2 domian in PLC-gamma recognize Tyr 1173 and is primary contributor to PLC-gamma association with the EGFR. Moreover stimulation of various GPCRs such as lysophosphatic acid (LPA) and endothelin-1 (ET-1) rapidly induce phosphorylation of adaptor protein Shc and Shc – Grb2 complex formation. Tyr 1173 on EGFR can function as a docking site for PLC-gamma and PI3-K (green arrow from yellow box). Furthermore Tyr 1173 interact with both SH2 and PTB domains in adoptor protein Shc plays major role in the Ras signalling and subsequence the EGF mediated activation of JNK which is dependent on Shc and controlling JNK activation and possible signalling pathways involved in MEKK1 activation and regulation of JNK and p38 MAPKs after EGF stimulation (red arrows show the signalling direction in the blue box).

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