Dermokine-β impairs ERK signaling through direct binding to GRP78.
Dermokine-β is abundant in stratified epithelia and in differentiating cultured keratinocytes. In this study, we investigated the role of dermokine-β in differentiation of keratinocytes. Treatment of keratinocytes or skin tumor cells with dermokine-β attenuated phosphorylation of extracellular-signal-regulated kinase (ERK). Exposure of cells to dermokine-β, 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-β-associated protein. Blockage of GRP78 expression by a specific siRNA abrogated actions of dermokine-β. These findings provide novel insights into the physiological significance of dermokine-β in the epidermis.
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka 554-8558, Japan. higashik2@sc.sumitomo-chem.co.jp
Kiyoshi
K
Higashi
Minoru
M
Hasegawa
Chikako
C
Yokoyama
Taro
T
Tachibana
Shinichi
S
Mitsui
Koichi
K
Saito
D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology; D007633:Keratins / Q000737:chemistry; D008954:Models, Biological; D010766:Phosphorylation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism*
C495568:DMKN protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D011506:Proteins; D007633:Keratins; D048049:Extracellular Signal-Regulated MAP Kinases