Related Experiment Video

Updated: May 9, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Epidermal hyperplasia induced by Raf-MAPK signaling requires Stat3 activation

Masahito Tarutani1, Kimiko Nakajima, Mikiro Takaishi

  • 1Department of Dermatology, Kochi Medical School, Kochi University, Kohasu, Okocho, Nankoku 783-8505, Japan.

Journal of Dermatological Science
|July 23, 2013
PubMed
Abstract

Insights

Stat3 signaling is essential for Raf-MAPK-driven epidermal hyperplasia, a condition mimicking psoriasis. Inhibiting Stat3 in mice significantly reduced skin thickening and inflammation, highlighting Stat3

Area of Science:

  • Dermatology
  • Molecular Biology
  • Oncology

Background:

  • Raf is a key downstream effector of Ras GTPases, regulating cell proliferation and differentiation via MAPK signaling.
  • Raf activation in mouse epidermis causes hyperplasia resembling squamous cell carcinoma and psoriasis.
  • Epidermal Stat3 activation is crucial for psoriasis development, as shown by keratinocyte-specific Stat3 activation models.

Purpose of the Study:

  • To investigate the role of Stat3 signaling in Raf-MAPK-dependent epidermal hyperplasia.

Main Methods:

  • K14-Raf:ER transgenic mice were crossed with epidermis-specific Stat3 null mice (K5-Cre.Stat3(flox/flox)).
  • The impact of Stat3 deficiency on Raf-induced epidermal hyperplasia was assessed in K5-Cre.Stat3(flox/flox) mice following 4-hydroxytamoxifen (4OHT) treatment.

Main Results:

  • Raf over-expression in K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice significantly attenuated epidermal hyperplasia and dermal infiltrates compared to controls.
  • Up-regulation of psoriasis-associated cytokines, including VEGF, was inhibited in Stat3-deficient mice after Raf induction.

Conclusions:

  • Raf-MAPK-dependent psoriatic-like epidermal hyperplasia necessitates Stat3 signaling within keratinocytes.
  • Stat3 is a critical mediator in the pathogenesis of Raf-induced skin conditions.
Keywords:
Epidermal hyperplasiaKnockout miceRafStat3Transgenic mice

More Related Videos

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Differentiation of Mouse Breast Epithelial HC11 and EpH4 Cells09:32

Differentiation of Mouse Breast Epithelial HC11 and EpH4 Cells

Published on: February 27, 2020

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...