Epidermal growth factor mitogenicity

Glasgow WC, Afshari CA, Barrett JC, Eling TE. Modulation of the epidermal growth factor mitogenic response by metabolites of linoleic and arachidonic acid in Syrian hamster embryo fibroblasts. Differential effects in tumor suppressor gene (+) and (-) phenotypes. J Biol Chem 1992 267 10771-10779. 

Extracellular factors that induce mitosis are termed mitogens. Some of these, such as epidermal growth factor (EOF) and fibroblast growth factor (FGF) are now being characterized. 

Carpenter, G. (1987). Receptors for epidermal growth factor and other polypeptide mitogens. Ann. Rev. Biochem. 56, 881—914. 

Simeonova, P. P. et al., c-Src-dependent activation of the epidermal growth factor receptor and mitogen-activated protein kinase pathway by arsenic. Role in carcinogenesis, J. Biol. Chem., 277, 2945, 2002. 

Cunnick, J.M., Dorsey, J.F., Standley, T., Turkson, J., Kraker, A.J., Fry, D.W., Jove, R., and Wu, J., 1998, Role of tyrosine kinase activity of epidermal growth factor receptor in the lysophosphatidic acid-stimulated mitogen-activated protein kinase pathway, J. Biol. Chem. 273 14468-14475. 

TP receptor signaling has been extensively docnmented in vascnlar smooth mns-cle and platelets, but its characterization in hnman ASM cells has been more limited until recently. ASM cells express messenger RNA (mRNA) for both TP receptor isoforms, and functional receptors respond to agonist with an increase in intracellular Ca " concentration (200). As a consequence, besides potentiating the epidermal growth factor (EGF) mitogenic response independently from transactivation of the EGF receptor (EGER) (200), TP receptor stimulation induces a concentration-dependent increase in DNA synthesis. 

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).

Witta SE, Gemmill RM, Hirsch FR et al. Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 2006 66 944-950. Walker F, Kato A, Gonez LJ et al. Activation of the Ras/mitogen-activated protein kinase pathway by kinase-defective epidermal growth factor receptors results in cell survival but not proliferation. Mol Cell Biol 1998 18 7192-7204. 

Figure 11-13 (A) A simplified version of the mitogen-activated kinase (MAPK) signaling cascade. At left is shown a hormone receptor, e.g., that for the epidermal growth factor (EGF). The receptor tyrosine kinase undergoes autophosphorylation on numerous tyrosines. The resulting phosphotyrosyl (Y-P) groups bind to SH2 domains of adapters such as Grb2 and She.

Jin, K., Mao, X. O., Del Rio Guerra, G., Jin, L., and Greenberg, D. A. (2005). Heparin-binding epidermal growth factor-like growth factor stimulates cell proliferation in cerebral cortical cultures through phosphatidylinositol S kinase and mitogen-activated protein kinase. J. Neurosci. Res. 81, 497-505. 

Eguchi, S., Numaguchi, K., Iwasaki, H., et al. 1998. Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J Biol Chem 273 8890-8896. 

Eguchi, S., Numaguchi, K., Iwasaki, H., Matsumoto, T., Yamakawa, T., Utsunomiya, H., Motley, E.D., Kawakatsu, H., Owada, K.M., Hirata, Y., Marumo, F., and Inagami, T. 1998. Calcium-dependent epidermal growth factor receptor transactivaiton mediates the angiotensin Il-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J. Biol. Chem. 273 8890-8896. 

Purdom, S., and Q.M. Chen. 2005. Epidermal growth factor receptor-dependent and - independent pathways in hydrogen peroxide-induced mitogen-activated protein kinase activation in car-diomyocytes and heart fibroblasts. J. Pharmacol. Exp. Ther. 312 1179-1186. 

Iwasaki H, Eguchi S, Ueno H, Marumo F, Hirata Y. 1999. Endothelin-mediated vascular growth requires p42/p44 mitogen-activated protein kinase and p70 S6 kinase cascades via transactivation of epidermal growth factor receptorl. Endocrinology 140 4659-4668. 

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