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Dermokine-β impairs ERK signaling through direct binding to GRP78

Kiyoshi Higashi1, Minoru Hasegawa, Chikako Yokoyama

  • 1Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka 554-8558, Japan. higashik2@sc.sumitomo-chem.co.jp

FEBS Letters
|June 28, 2012
PubMed

Insights

Dermokine-β plays a key role in skin cell differentiation by regulating extracellular-signal-regulated kinase (ERK) signaling. This protein interacts with glucose-regulated protein 78 (GRP78), influencing keratinocyte differentiation and gene expression.

Area of Science:

  • Dermatology
  • Cell Biology
  • Biochemistry

Background:

  • Dermokine-β is a protein found in stratified epithelia and differentiating keratinocytes.
  • Its specific role in keratinocyte differentiation requires further investigation.

Purpose of the Study:

  • To elucidate the function of dermokine-β in keratinocyte differentiation.
  • To identify molecular mechanisms underlying dermokine-β's actions.

Main Methods:

  • Treatment of keratinocytes and skin tumor cells with dermokine-β and its peptide.
  • Analysis of extracellular-signal-regulated kinase (ERK) phosphorylation.
  • Gene expression analysis.
  • Chemical cross-linking, immunoprecipitation, and proteomics to identify interacting proteins.
  • RNA interference (siRNA) to block glucose-regulated protein 78 (GRP78) expression.

Main Results:

  • Dermokine-β treatment attenuated ERK phosphorylation in keratinocytes and skin tumor cells.
  • Dermokine-β and its peptide interrupted ERK phosphorylation and stimulated dermokine gene expression.
  • Inhibition of ERK signaling enhanced dermokine expression.
  • Glucose-regulated protein 78 (GRP78) was identified as a dermokine-β-associated protein.
  • siRNA-mediated blockage of GRP78 abrogated dermokine-β's effects.

Conclusions:

  • Dermokine-β regulates keratinocyte differentiation through modulation of ERK signaling.
  • The interaction between dermokine-β and GRP78 is crucial for its biological functions in the epidermis.
  • These findings offer new insights into the physiological significance of dermokine-β in skin biology.

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