Open AccessTransglutaminase down‐regulates the dimerization of epidermal growth factor receptor in rat perivenous and periportal hepatocytes
Author(s) -
Maruko A.,
Ohtake Y.,
Katoh S.,
Ohkubo Y.
Publication year - 2009
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2009.00622.x
Subject(s) - autophosphorylation , phosphorylation , epidermal growth factor , epidermal growth factor receptor , tissue transglutaminase , hepatocyte , western blot , receptor , biology , microbiology and biotechnology , chemistry , biochemistry , cancer research , protein kinase a , in vitro , enzyme , gene
Objective: Recently, we found that transglutaminase 2 (TG2) might be involved in the difference in proliferative capacities between periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) through down‐regulation of high‐affinity epidermal growth factor receptor (EGFR). However, it is uncertain whether this high‐affinity EGFR contributes to the hepatocyte growth signalling pathway. Here, we have investigated the influence of TG2 on EGF‐induced EGFR dimerization and its phosphorylation, which are important steps in the hepatocyte proliferative/growth signalling pathway, in PPH and PVH. Materials and methods: PPH and PVH were isolated using the digitonin/collagenase perfusion technique. Amounts of TG2, EGFR dimerization and its phosphorylation were determined by Western blot analysis. Results: Pretreatment with monodansylcadaverine, an inhibitor of TG2, greatly increased EGF‐induced EGFR dimerization and its phosphorylation in PVH compared with PPH. Conversely, treatment with retinoic acid, an inducer of TG2, significantly decreased EGF‐induced EGFR dimerization and its phosphorylation with a significant increase in TG2 expression and its catalysed products, isopeptide bonds, in both subpopulations. It was found that EGFR served as a substrate for TG2. Conclusion: The present data showed good correlation with our previous data on EGF‐induced DNA synthesis and EGFR‐binding affinity to EGF. These results suggest that zonal difference in cell growth between PPH and PVH may be caused by down‐regulation of EGFR dimerization and subsequent autophosphorylation through TG2‐mediated cross‐linking of EGFR.