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Epidermal growth factor (EGF) stimulates inositol trisphosphate formation in cells which overexpress the EGF receptor
Authors:M I Wahl  J D Sweatt  G Carpenter
Affiliation:1. Division of Cardiovascular Medicine, The Gill Heart and Vascular Institute, University of Kentucky, Lexington, KY 40536, United States of America;2. Veterans Affairs Medical Center, Lexington, KY 40511, United States of America;1. iMed.ULisboa - Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, Lisboa 1649-003, Portugal;2. Centro de Química e Bioquímica (CQB) e Centro de Química Estrutural (CQE), Faculdade de Ciências, Universidade de Lisboa, Ed. C8, Campo Grande, Lisboa 1749-016, Portugal;3. Sir Martin Evans Building, School of Biosciences, Cardiff University, Cardiff, UK;4. Centro de Química-Física Molecular - Institute of Nanoscience and Nanotechnology (CQFM-IN), IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal;5. Institute for Clinical Chemistry, University Hospital Zurich, Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland
Abstract:EGF is a low molecular weight polypeptide hormone which acts as a regulator of cell growth and differentiation. The A-431 cell line has been used frequently to examine receptor-mediated biochemical effects of EGF, since this cell line has an increased (20-50 fold) level of EGF receptors. We have utilized A-431 cells to examine the influence of EGF on formation of an intracellular second messenger, inositol, 1,4,5-trisphosphate (Ins-1,4,5-P3), and other inositol phosphates. The results show that EGF induces rapid formation of Ins-1,4,5-P3 as well as Ins-1,3,4-P3 and Ins-1,3,4,5-P4. There is a concurrent decrease in the level of the lipid precursor for Ins-1,4,5-P3, phosphatidylinositol 4,5-biphosphate (PIP2). Furthermore, we have examined five other cell lines that overexpress the EGF receptor and find that EGF treatment induces formation of inositol polyphosphates in those cell lines also.
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