Stem cell factor induces ERM proteins phosphorylation through PI3K activation to mediate melanocyte proliferation and migration.
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.
Jeon
Songhee
S
Dongguk University Research Institute of Biotechnology, Medical Science Research Center, Dongguk University School of Medicine, South Korea.
Kim
Nan-Hyung
NH
Kim
Ji-Young
JY
Lee
Ai-Young
AY
D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D019089:Stem Cell Factor / Q000502:physiology*; D013912:Threonine / Q000737:chemistry / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019869:Phosphatidylinositol 3-Kinases; D019089:Stem Cell Factor; D013912:Threonine; D020830:rac1 GTP-Binding Protein; D000099149:Ezrin; C071058:moesin; C071776:radixin