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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Related Experiment Video

Updated: Dec 11, 2025

Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
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The KEAP1/NRF2 Signaling Pathway in Keratinization.

Yosuke Ishitsuka1, Tatsuya Ogawa1, Dennis Roop2

  • 1Department of Dermatology, Faculty of Medicine, University of Tsukuba 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Antioxidants (Basel, Switzerland)
|August 23, 2020
PubMed
Summary
This summary is machine-generated.

Aberrant keratinization underlies skin disorders. Sulfur metabolism, regulated by the KEAP1/NRF2 pathway, provides cytoprotection and insights into skin disease mechanisms.

Keywords:
KEAP1/NRF2 signalingdisulfideenvironmental responsegene expression regulationkeratinizationloricrinsquamous epitheliumthiol

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Area of Science:

  • Biochemistry
  • Dermatology
  • Molecular Biology

Background:

  • Aberrant keratinization is linked to skin conditions like psoriasis and atopic dermatitis.
  • Gene-environment interactions influence disease phenotypes.
  • The KEAP1/NRF2 pathway regulates environmental responses in squamous epithelia.

Purpose of the Study:

  • To explore the role of sulfur metabolism in keratinization and cytoprotection.
  • To review the KEAP1/NRF2 signaling pathway in epidermal differentiation.
  • To understand gene-environment interactions in skin health and disease.

Main Methods:

  • Analysis of keratinization processes.
  • Investigation of the KEAP1/NRF2 signaling pathway.
  • Utilizing insights from mouse models with Keap1-null mutations.

Main Results:

  • Sulfur metabolism is crucial for cytoprotection in mammals.
  • The KEAP1/NRF2 pathway acts as a thiol-based sensor-effector system.
  • Mouse models reveal implications for keratinization pathomechanisms.

Conclusions:

  • Understanding keratinization and the KEAP1/NRF2 pathway offers insights into skin disorders.
  • Sulfur metabolism's role in cytoprotection is significant for terrestrial mammals.
  • This knowledge can advance the study of innate integumentary defense systems.