Dermokine-beta impairs ERK signaling through direct binding to GRP78

作者：Higashi Kiyoshi^*; Hasegawa Minoru; Yokoyama Chikako; Tachibana Taro; Mitsui Shinichi; Saito Koichi

来源：FEBS Letters, 2012, 586(16): 2300-2305.

DOI：10.1016/j.febslet.2012.06.022

• Dermokine-beta
• Keratinocyte
• Differentiation
• ERK1/2
• GRP78

Dermokine-beta is abundant in stratified epithelia and in differentiating cultured keratinocytes. In this study, we investigated the role of dermokine-beta in differentiation of keratinocytes. Treatment of keratinocytes or skin tumor cells with dermokine-beta attenuated phosphorylation of extracellular-signal-regulated kinase (ERK). Exposure of cells to dermokine-beta, as well as its carboxyl-terminus domain peptide, interrupted phosphorylation of ERK and stimulated dermokine gene expression. Inhibition of ERK signaling by its specific inhibitor also increased dermokine expression level. A combination of chemical cross-linking and immunoprecipitation, followed by proteomics analyses, identified glucose-regulated protein 78 (GRP78) as a dermokine-beta-associated protein. Blockage of GRP78 expression by a specific siRNA abrogated actions of dermokine-beta. These findings provide novel insights into the physiological significance of dermokine-beta in the epidermis.

• 出版日期2012-7-30