EGF Triggers a Similar Signalling Cascade in Different Cell Types Overexpressing the EGF Receptor
The mechanism by which growth factors stimulate mitogenesis upon binding to their receptors involves several biochemical events and the generation of intracellular second messengers. EGF1 is regarded as a classical example of a growth factor which acts on a receptor harboring tyrosine kinase activity (Berridge, 1987 a,b; Carpenter, 1987). Recently, several reports have indicated that in certain cell types, EGF stimulates inositol lipid turnover with the formation of Ca2+- mobilizing inositol polyphosphates and 1,2-diacylglycerol activating protein kinase C (Hepler et al, 1987; Pandiella et al., 1987; Johnson and Garrison, 1987; Earp et al., 1988; Takasu et al., 1988; Moscat et al., 1988). However, other studies demonstrated that EGF was unable to trigger phosphoinositide metabolism in 3T3 fibroblasts and in a clone of A431 carcinoma cells (Besterman et al, 1986; Macara, 1986; Wakelam et al., 1986; Pandiella et al, 1987). Therefore, EGFinduced inositol lipid turnover might be considered lineagespecific, or at least cell type-specific (Earp et al., 1988), and the role of phosphoinositide metabolism in EGF-induced mitogenesis remains to be established.
KeywordsSerotonin Vanadate Sarcoma Angiotensin Prostaglandin
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- Earp, H. S., Hepler, J.R., Petch, L. A., Miller, A., Berry, A., Harris, J., Raymond, V.W., McCune, B.K., Lee, L. W., Grisham, J.W., and Harden, T. K. (1988) Epidermal growth factor (EGF) and hormone stimulate phosphoinositide hydrolysis and increase EGF receptor protein synthesis and mRNA levels in rat liver epithelial cells. J. Biol. Chem., 263:13868.PubMedGoogle Scholar
- Finzi, E., Fleming, T. P., Segatto, O., Pennington, C. Y. Bringman, T. S., Derynck, R., and Aaronson, S. A. (1987) The human transforming growth factor type alpha coding sequence is not a direct-acting oncogene when overexpressed in NIH/3T3 cells. Proc. Natl. Acad. Sci. USA, 84:3733.PubMedCrossRefGoogle Scholar
- Hawkins, P. T., Stephens, L., and Downes, C. P. (1986) Rapid formation of inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in rat parotid glands may both result indirectly from receptor-stimulated release of inositol 1,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. Biochem. J., 238, 507.PubMedGoogle Scholar
- Hepler, J. R., Nakahata, N., Lovenberg, T. W., DiGuiseppi, J., Herman, B., Earp, H. S., and Harden T. K. (1987) Epidermal growth factor stimulates the rapid accumulation of inositol (1,4,5)-trisphosphate and a rise in cytosolic calcium mobilized from intracellular stores in A431 cells. J. Biol. Chem., 262:2951.PubMedGoogle Scholar
- Lapetina, E.G.: Inositide-dependent and independent mechanisms in platelet activation. In “Phosphoinositides and Receptor Mechanisms” pp. 271–286, 1986, Alan R. Liss Inc. (New York, NY USA).Google Scholar