Effect of EGF on [3H]-thymidine incorporation and cell cycle regulatory proteins in primary cultured chicken hepatocytes: Involvement of Ca2+/PKC and MAPKs.

The reported studies on the metabolism in chicken hepatocytes in comparison with those of mammals are quite different. Therefore, this study examined the effect of EGF on DNA synthesis along with its related signal cascades in primary cultured chicken hepatocytes. EGF stimulated DNA synthesis in a dose (> or =10 ng/ml)-dependent manner, which correlated with the increase in CDK-2 and CDK-4 expression. The EGF-induced increase in [3H]-thymidine incorporation was blocked by AG 1478 (an EGF receptor tyrosine kinase antagonist), genistein, and herbimycin A (tyrosine kinase inhibitors), suggesting a role in the activation and tyrosine phosphorylation of the EGF receptor. In addition, the EGF-induced stimulation of [3H]-thymidine incorporation was prevented by staurosporine, H-7, or bisindolylmaleimide I (protein kinase C inhibitors), suggesting a role of PKC. In addition, PD 98059 (a MEK inhibitor), SB 203580 (a p38 MAPK inhibitor), and SP 600125 (a JNK inhibitor) blocked the EGF-induced stimulation of [3H]-thymidine incorporation and CDK-2/4 expression. Indeed, EGF increased the translocation of PKC from the cytosol to the membrane fraction, and increased the activation of p44/42 MAPK, p38 MAPK, and JNK. Moreover, EGF increased the CDK-2, CDK-4, cyclin D1, and cyclin E expression levels but decreased the p21 and p27 expression levels. These EGF-induced increases were blocked by an EGF receptor antagonist, tyrosine kinase inhibitors, PKC inhibitors, and MAPKs inhibitors. In conclusion, EGF stimulates DNA synthesis of primary cultured chicken hepatocytes via Ca2+/PKC and the MAPKs signaling pathways.

Lee MY ，Lee SH ，Kim YH ，Heo JS ，Park SH ，Lee JH ，Han HJ ... -  《JOURNAL OF CELLULAR BIOCHEMISTRY》

A potential mechanism for short time exposure to hypoxia-induced DNA synthesis in primary cultured chicken hepatocytes: Correlation between Ca(2+)/PKC/MAPKs and PI3K/Akt/mTOR.

Lee SH ，Lee MY ，Lee JH ，Han HJ ... -  《-》

EGF-induced inhibition of glucose transport is mediated by PKC and MAPK signal pathways in primary cultured chicken hepatocytes.

Lee MY ，Park SH ，Lee YJ ，Heo JS ，Lee JH ，Han HJ ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY》

Albumin-stimulated DNA synthesis is mediated by Ca2+/PKC as well as EGF receptor-dependent p44/42 MAPK and NF-kappaB signal pathways in renal proximal tubule cells.

Lee YJ ，Han HJ 《-》

L-leucine increases [3H]-thymidine incorporation in chicken hepatocytes: involvement of the PKC, PI3K/Akt, ERK1/2, and mTOR signaling pathways.

Lee MY ，Jo SD ，Lee JH ，Han HJ ... -  《-》