Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Calcium-induced Human Keratinocytes(HaCaT) Differentiation Requires Protein Kinase B Activation in Phosphatidylinositol 3-Kinase-dependent Manner

  • Piao, Longzhen (Cell Signaling Laboratory Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Shin, Sang-Hee (Cell Signaling Laboratory Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Yang, Keum-Jin (Cell Signaling Laboratory Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Park, Ji-Soo (Department of Pharmacology, College of Medicine, Chungnam National University) ;
  • Shin, Eul-Soon (Department of Clinical Pathology, College of Medicine, Chungnam National University) ;
  • Li, Yu-Wen (Cell Signaling Laboratory Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Park, Kyung-Ah (Department of Dermatology, College of Medicine, Chungnam National University) ;
  • Byun, Hee-Sun (Department of Dermatology, College of Medicine, Chungnam National University) ;
  • Won, Min-Ho (Department of Dermatology, College of Medicine, Chungnam National University) ;
  • Lee, Choong-Jae (Department of Dermatology, College of Medicine, Chungnam National University) ;
  • Hur, Gang-Min (Department of Dermatology, College of Medicine, Chungnam National University) ;
  • Seok, Jeong-Ho (Department of Dermatology, College of Medicine, Chungnam National University) ;
  • Kim, Ju-Duck (Department of Pharmacology, College of Medicine, Chungnam National University)
  • Published : 2006.09.30
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Abstract

The survival and growth of epithelial cells depends on adhesion to the extracellular matrix. An adhesion signal may regulate the initiation of differentiation, since epidermal keratinocytes differentiate as they leave the basement membrane. A metabolically dead cornified cell envelope is the end point of epidermal differentiation so that this process may be viewed as a specialized form of programmed cell death. In order to investigate the precise cellular signaling events loading to terminal differentiation of keratinocytes, we have utilized HaCaT cells to monitor the biological consequences of $Ca^{2+}$ stimulation and numerous downstream signaling pathways, including activation of the extracellular signal-regulated protein kinase(ERK) pathway and activation of phosphatidylinositol 3-kinase(PI3K). The results presented in this study show that $Ca^{2+}$ function as potent agents for the differentiation of HaCaT keratinocytes, and this differentiation depends or the activation of ERK, Protein kinase B(PKB) and p70 ribosomal protein S6 kinase(p70S6K). Finally, the results show that the expression of Activator protein 1(AP-1; c-Jun and c-Fos) increased following $Ca^{2+}$-mediated differentiation of HaCaT cells, suggesting that ERK-mediated AP-1 expression is critical for initiating the terminal differentiation of keratinocytes.

Keywords

References

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