Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stem cell factor (SCF) and endothelin-3 (ET3) are both necessary for melanocyte development. In order to obtain immortal cell populations of melanoblasts that can survive without feeder cells, we first obtained an immortal cell population of neural crest cells (NCCs) from Sl/+ and +/+ mice of strain WB by incubating with a culture medium supplemented with SCF and ET3, and then we designated them as NCC-SE3 cells. NCC-SE3 cells were bipolar, polygonal, or round in shape and possessed melanosomes of stages I-III (mainly stage I). They were positive to dihydroxyphenylalanine (DOPA) reaction and expressed KIT (a receptor tyrosine kinase), tyrosinase, tyrosinase-related protein-1 (TRP1), tyrosinase-related protein-2 (TRP2), and endothelin-B receptor (ETRB) as determined by immunostaining. We next cultured NCC-SE3 cells by changing culture medium from the one supplemented with SCF + ET3 to the one supplemented with SCF or ET3. NCC-SE3 cells cultured with ET3 alone, designated as NCC-E3 cells, were bipolar in shape and had mainly stage II melanosomes and expressed the same proteins as did NCC-SE3 cells. However, NCC-SE3 cells cultured with SCF alone, designated as NCC-S4.1 cells, were polygonal in shape and had mainly stage I melanosomes. They are thought to be more immature because they were positive to KIT, TRP1, and TRP2, but not to ETR(B), tyrosinase, and DOPA reaction. When 12-O-tetradecanoylphorbol 13-acetate and cholera toxin were added to the culture medium, NCC-S4.1 cells changed shape from polygonal to bipolar and became DOPA-positive. This suggests that NCC-S4.1 cells are melanoblasts that have the potential to differentiate into melanocytes. These cell populations will be extremely useful to study factors that affect melanocyte development and melanogenesis.
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PMID:Stem cell factor and/or endothelin-3 dependent immortal melanoblast and melanocyte populations derived from mouse neural crest cells. 1104 61

The teleost Xiphophorus provides a genetically well-described model system to study the molecular processes underlying melanoma formation. As transcriptional deregulation is a widespread phenomenon in many tumors, we have studied the regulation of melanoma-specific gene expression in this fish. A central regulator of melanocyte specific gene expression, which is also a marker for melanomas, is the transcription factor microphthalmia-associated transcription factor (MITF). One of its targets, the tyrosinase gene, codes for a key enzyme in the melanin synthesis pathway. We could show that the promoter of the medaka tyrosinase gene is highly active in the Xiphophorus melanoma cell line PSM (platyfish-swordtail melanoma) but not in non-melanoma cells. Functional dissection of the promoter revealed that three E-boxes are essential for its pigment cell-specific activity. These binding sites for basic helix-loop-helix transcription factors are recognized by a nuclear protein from the melanoma cell line PSM, most likely MITF, as its exogenous delivery could activate the promoter in non-melanoma cells. The use of specific signalling inhibitors demonstrated that the activity of the tyrosinase promoter is negatively regulated by the melanoma-inducing receptor tyrosine kinase Xmrk in PSM cells. This repression is mediated by MAPkinase and dependent on E-box integrity, again implicating the involvement of MITF. The cumulative evidence indicates that in Xiphophorus, Xmrk suppresses differentiation signals relayed by MITF as part of the transformation process finally resulting in melanoma formation.
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PMID:MITF-M plays an essential role in transcriptional activation and signal transduction in Xiphophorus melanoma. 1459 95

We developed a method to efficiently ablate a single cell type, the zebrafish melanocyte, and study the mechanisms of its regeneration. We found that a small molecule, (2-morpholinobutyl)-4-thiophenol (MoTP), specifically ablates zebrafish larval melanocytes or melanoblasts, and that this melanocytotoxicity is dependent on tyrosinase activity, which presumably converts MoTP to cytotoxic quinone species. Following melanocyte ablation by MoTP treatment, we demonstrate by BrdU incorporation experiments that regenerated melanocytes are derived from the division of otherwise quiescent melanocyte precursors or stem cells. We further show that larval melanocyte regeneration requires the kit receptor tyrosine kinase. Our results suggest that a small number of melanocyte precursors or stem cells unevenly distributed in larvae are drawn upon to reconstitute the larval melanocyte population following melanocyte ablation by MoTP.
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PMID:Small molecule-induced ablation and subsequent regeneration of larval zebrafish melanocytes. 1691 96

It is well established that cell-intrinsic signaling through the receptor tyrosine kinase KIT is critical for the development of neural crest-derived melanocytes. Nevertheless, it is not entirely clear whether Kit acts exclusively in a melanocyte-autonomous manner or in addition indirectly through other cell types. To address this question in vivo, we generated a targeted allele of Kit that allowed for CRE recombinase-mediated deletion of the transmembrane domain of KIT. Mice carrying one copy of the targeted allele and expressing CRE under the melanoblast/melanocyte-specific tyrosinase promoter exhibited a white spotting phenotype that was even more extensive compared with that found in mice heterozygous for a Kit-null allele. This phenotype is unlikely the result of sequestration of KIT ligand by neighboring cells or by potentially secreted forms of KIT because the spotting phenotype could not be rescued by overexpression of KITL. Likewise, overexpression of endothelin-3 or hepatocyte growth factor was unable to rescue melanocytes in these mice. Although the severity of the observed phenotype remains to be explained, the findings indicate that melanocyte-selective impairment of Kit is sufficient to interfere with normal melanocyte development.
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PMID:Conditional Deletion of Kit in Melanocytes: White Spotting Phenotype Is Cell Autonomous. 2573 11