Signal transduction epidermal growth factor

Figure 43-13. Several signal transduction pathways converge on CBP/p300. Ligands that associate with membrane or nuclear receptors eventually converge on CBP/p300. Several different signal transduction pathways are employed. EGF, epidermal growth factor GH, growth hormone PrI, prolactin TNF, tumor necrosis factor other abbreviations are expanded in the text.

Fig. 6. Role of signal transduction pathways in phosphorylating H3 at Ser-10 and Ser-28. The Ras-MAPK (mitogen activated protein kinase) pathway is activated by EGF (epidermal growth factor) and TPA (12-0-tetradecanoylphorbol-13-acetate). UV-B activates both the Ras-MAPK pathway and the p38 kinase pathway (for more information about the signal transduction pathways see http // kinase, oci.utoronto.ca/signallingmap.html).

Phosphorylation of H3 is not limited to mitosis and also occurs in G1 phase of the cell cycle. Activation of the Ras-Raf-MEK-ERK signal transduction pathway and/or of the p38 stress kinase pathway when cells are treated with epidermal growth factor (EGF), 12-G-tetradecanoylphorbol-13-acetate (TPA), anesomycin, okadiac acid, and stresses such as UV irradiation induces the rapid phosphorylation of H3 at Ser-10 and/or Ser-28 [68-72] (Figs. 5 and 6). Inhibition of the MEK1,2 activity with PD98059 prevents the activation of ERK and TPA-induced H3... 

Further examples of substrates of protein kinase C are the epidermal growth factor receptor (see Chapter 8), a Na7H exchanger protein, and Raf kinase (Chapter 9). Activation of protein kinase C may, as the examples show, act on other central signal transduction pathways of the cell it may have a regulating activity on transcription processes and it is involved in the regulation of transport processes. Many substrates of protein kinase C are membrane proteins and it is evident that membrane association of protein kinase C is of great importance for the phosphorylation of these proteins. 

Inhibition of Epidermal Growth Factor Receptor (EGFR)-Mediated Pathways 175 Inhibition of Insulin-like Growth Factor (IGF)-I Mediated Signal Transduction Pathway 175... 

Prenzel N, Fischer OM, Streit S, Hart S, Ullrich A. 2001. The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Relat Cancer 8 11-31. 

Nicholas MK, Lukas RV, Jafri NF, Faoro L, Salgia R (2006) Epidermal growth factor receptor -mediated signal transduction in thedevelopment and therapy of gliomas. Clin Cancer Res 12 7261-7270... 

Resat H, Ewald JA, Dixon DA, Wiley HS. An integrated model 93. of epidermal growth factor receptor trafficking and signal transduction. Biophys. J. 2003 85 730-743. 94. 

---