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Updated: Jun 28, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Stem cell factor induces ERM proteins phosphorylation through PI3K activation to mediate melanocyte proliferation and
Songhee Jeon1, Nan-Hyung Kim, Ji-Young Kim
1Dongguk University Research Institute of Biotechnology, Medical Science Research Center, Dongguk University School of Medicine, South Korea.
Abstract:
Stem cell factor (SCF) activates a variety of signals associated with stimulation of proliferation, differentiation, migration, and survival in melanocytes. However, the molecular mechanisms by which SCF and its receptor Kit activates these signaling pathways simultaneously and independently are still poorly defined. Here, we examined whether SCF induces ezrin/radixin/moesin (ERM) proteins phosphorylation as a downstream target of PI3K in melanocytes. ERM proteins are cross-linkers between the plasma membrane and the actin cytoskeleton and are activated by phosphorylation of a C-terminal threonine residue. Our results demonstrated that SCF-induced ERM proteins phosphorylation on threonine residue and Rac1 activation in cultured normal human melanocytes through the activation of PI3K. The functional role of phosphorylated-ERM proteins was examined using melanocytes infected with adenovirus carrying a dominant negative mutant (Ala-558, TA) or wild type of moesin. In the TA moesin-overexpressing melanocytes, SCF-induced cell proliferation and migration were inhibited. Thus, our results indicate that phosphorylation of ERM proteins plays an important role in the regulation of SCF-induced melanocyte proliferation and migration.
Insights
Stem cell factor (SCF) triggers melanocyte growth and movement by activating PI3K, which phosphorylates ezrin/radixin/moesin (ERM) proteins. Inhibiting ERM proteins blocks SCF-driven proliferation and migration, highlighting their crucial role.
Area of Science:
- Cell Biology
- Dermatology
- Molecular Biology
Background:
- Stem cell factor (SCF) and its receptor Kit are crucial for melanocyte function, regulating proliferation, differentiation, migration, and survival.
- The precise molecular mechanisms by which SCF/Kit signaling pathways are activated remain incompletely understood.
- Ezrin/radixin/moesin (ERM) proteins link the plasma membrane to the actin cytoskeleton and are activated by phosphorylation.
Purpose of the Study:
- To investigate whether SCF induces ezrin/radixin/moesin (ERM) protein phosphorylation via PI3K signaling in melanocytes.
- To elucidate the role of ERM protein phosphorylation in SCF-mediated melanocyte proliferation and migration.
Main Methods:
- Cultured normal human melanocytes were treated with SCF.
- PI3K activation and ERM protein phosphorylation were assessed.
- Rac1 activation was measured.
- Melanocytes were infected with adenovirus expressing dominant-negative or wild-type moesin mutants.
- SCF-induced proliferation and migration were evaluated in moesin-overexpressing cells.
Main Results:
- SCF treatment activated PI3K and induced ERM protein phosphorylation at a C-terminal threonine residue in melanocytes.
- SCF also led to Rac1 activation.
- Overexpression of a dominant-negative moesin mutant inhibited SCF-induced melanocyte proliferation and migration.
- Wild-type moesin overexpression did not inhibit these processes.
Conclusions:
- SCF-induced ERM protein phosphorylation, mediated by PI3K activation, is a key event in regulating melanocyte proliferation and migration.
- Phosphorylated ERM proteins are essential downstream effectors of SCF signaling in melanocytes.
- Targeting ERM protein phosphorylation may offer therapeutic strategies for conditions involving melanocyte migration and proliferation.
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