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KMID : 0379520060220030283
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한국독성학회지
2006 Volume.22 No. 3 p.283 ~ p.291
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Calcium-induced Human Keratinocytes(HaCaT) Differentiation Requires Protein Kinase B Activation in Phosphatidylinositol 3-Kinase-dependent Manner
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Piao Long-Zhen
Shin Sang-Hee
Yang Keum-Jin
Park Ji-Soo
Shin Eul-Soon
Li Yu-Wen
Park Kyung-Ah
Byun Hee-Soon
Won Min-Ho
Lee Choong-Jae
Hur Gang-Min
Seok Jeong-Ho
Kim Ju-Duck
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Abstract
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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.
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KEYWORD
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Terminal differentiation, Keratinocytes, HaCaT cell, PI3K, PKB, S6
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