Altered regulation of EGF receptor signaling following a partial hepatectomy

Journal of Cellular Physiology
E SkarpenH S Huitfeldt

Abstract

We have studied epidermal growth factor receptor (EGFR) phosphorylation and localization in the pre-replicative phase of liver regeneration induced by a 70% partial hepatectomy (PH), and how a PH affects EGFR activation and trafficking. When Western blotting was performed on livers after PH with antibodies raised against activated forms of EGFR autophosphorylation sites, no marked increase in EGFR tyrosine phosphorylation was observed. However, events associated with attenuation of EGFR signals were observed. Two hours after PH, we found increased EGFR ubiquitination and internalization, followed by receptor downregulation. Furthermore, EGFR phosphorylation following an injection of EGF was reduced after PH. This reduction correlated with an increased activation of PKC and a distinct augmentation in the phosphorylation of the PKC-regulated T654-site of EGFR. When primary cultured hepatocytes were treated with tetradecanoylphorbol acetate (TPA) to induce T654-phosphorylation of EGFR, we found colocalization of a fraction of EGFR with EEA1, downregulation of EGF-mediated EGFR autophosphorylation, altered ligand-induced intracellular sorting of EGFR, and increased mitogenic signaling through the EGFR-Ras-Raf-ERK pathway. Further, ...Continue Reading

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Citations

Aug 12, 2008·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Amrita KamatMichael S Katz
Aug 28, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Judit López-LuqueIsabel Fabregat
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Jun 20, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Min Young LeeHo Jae Han
Jul 16, 2011·The Korean Journal of Hepatology·Seon Ok MinKyung Sik Kim
Nov 22, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lawrence A SchevingWilliam E Russell
May 13, 2006·Molecular and Cellular Biochemistry·Rafał Pawlowski, Jolanta Jura

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