Coordinated mRNA expression of c-Kit with tyrosinase and TRP-1 in melanin pigmentation of normal and malignant human melanocytes and transient activation of tyrosinase by Kit/SCF-R.
The proto-oncogene c-Kit encodes a membrane receptor protein with intrinsic tyrosine kinase activity. Activation of c-Kit induces cell proliferation, differentiation or migration among different cell types. The present study provides evidence that c-Kit plays an important role in the cell differentiation rather than in cell proliferation in pigment cells. We found that normal human melanocytes and a limited number of melanoma cells, e.g. WM35, WM39 and G361 cell lines, expressed the c-Kit gene together with tyrosinase and TRP-1 genes. When exposed to alpha-melanocyte stimulating hormone, these three cell lines also showed an increased tyrosinase (dopa-oxidase) activity. By incubating these cells with 20 ng/ml of stem cell factor (SCF) which is a ligand of c-Kit receptor, we found a transient increase of tyrosinase activity 2-4 h post-incubation, indicating an early response of tyrosinase activation, either by elevating tyrosinase protein expression or by tyrosinase protein modification (e.g. phosphorylation). However, Western blot analysis using anti-tyrosinase antibody suggested that there was no change of tyrosinase protein expression between SCF-treated and non-treated cells. We therefore suggest that protein modulation of tyrosinase (e.g. phosphorylation) plays an important role in c-Kit-induced melanogenesis.
Faculty of Medicine, University of Alberta, Edmonton, Canada.
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D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases; D010858:Pigmentation; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019089:Stem Cell Factor / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D019089:Stem Cell Factor; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D019009:Proto-Oncogene Proteins c-kit