CEACAM1 modulates epidermal growth factor receptor–mediated cell proliferation
| Autor: | Denisa May, Holger Kalthoff, Qusai Y. Al-Share, George A. Abou-Rjaily, Sue-Hwa Lin, Michael Neumaier, Randall J. Ruch, Anthony M. DeAngelis, Sang Jun Lee, Sonia M. Najjar |
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| Rok vydání: | 2004 |
| Předmět: |
Male
MAPK/ERK pathway Cell division MAP Kinase Signaling System Recombinant Fusion Proteins medicine.medical_treatment Adipose tissue Mice Transgenic Biology Article Mice Antigens CD Cell Line Tumor medicine Animals Humans Insulin Obesity Epidermal growth factor receptor Cell adhesion molecule Cell growth Growth factor General Medicine Antigens Differentiation Carcinoembryonic Antigen Rats Cell biology ErbB Receptors Liver COS Cells Cancer research biology.protein Phosphorylation Cell Adhesion Molecules Cell Division |
| Zdroj: | Journal of Clinical Investigation. 114:944-952 |
| ISSN: | 0021-9738 |
| Popis: | Phosphorylation of the cell adhesion protein CEACAM1 increases insulin sensitivity and decreases insulin-dependent mitogenesis in vivo. Here we show that CEACAM1 is a substrate of the EGFR and that upon being phosphorylated, CEACAM1 reduces EGFR-mediated growth of transfected Cos-7 and MCF-7 cells in response to EGF. Using transgenic mice overexpressing a phosphorylation-defective CEACAM1 mutant in liver (L-SACC1), we show that the effect of CEACAM1 on EGF-dependent cell proliferation is mediated by its ability to bind to and sequester Shc, thus uncoupling EGFR signaling from the ras/MAPK pathway. In L-SACC1 mice, we also show that impaired CEACAM1 phosphorylation leads to ligand-independent increase of EGFR-mediated cell proliferation. This appears to be secondary to visceral obesity and the metabolic syndrome, with increased levels of output of free fatty acids and heparin-binding EGF-like growth factor from the adipose tissue of the mice. Thus, L-SACC1 mice provide a model for the mechanistic link between increased cell proliferation in states of impaired metabolism and visceral obesity. |
| Databáze: | OpenAIRE |
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