Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used a probe derived from TRP-2/DT to detect migratory melanoblasts shortly after they emerge from the neural crest, as early as 10 days post coitum (dpc). TRP-2/DT expression is otherwise restricted to the presumptive pigmented retinal epithelium, the developing telencephalon and the endolymphatic duct. The pattern of steel and c-kit hybridisation in the developing brain differed from that of TRP-2. TRP-1 and tyrosinase probes also detected melanoblasts but were both expressed later in development than TRP-2. We used the TRP-2/DT probe to investigate the way that the Steel-dickie (Sld) mutation interferes with melanocyte development, and found that the membrane-bound steel growth factor which is missing in Sld/Sld mutants is necessary for the survival of melanoblasts but not for their early migration and initial differentiation.
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PMID:TRP-2/DT, a new early melanoblast marker, shows that steel growth factor (c-kit ligand) is a survival factor. 128 May 58

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.
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PMID: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. 854 20

The development of melanocytes, which are pigment-producing cells responsible for skin, hair, and eye color, is absolutely dependent on the action of the microphthalmia basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor (Mi); mice lacking a functional Mi protein are entirely devoid of pigment cells. Mi has been shown to activate transcription of the tyrosinase, TRP-1, TRP-2, and QNR-71 genes through specific E-box elements, most notably the highly conserved M box. We investigated the mechanism which enables Mi to be recruited specifically to a restricted subset of E boxes in target promoters while being prevented from binding E-box elements in other promoters. We show both in vitro and in vivo that the presence of a T residue flanking a CATGTG E box is an essential determinant of the ability of Mi to bind DNA, and we successfully predict that the CATGTG E box from the P gene would not bind Mi. In contrast, no specific requirement for the sequences flanking a CACGTG E box was observed, and no binding to an atypical E box in the c-Kit promoter was detected. The relevance of these observations to the control of melanocyte-specific gene expression was highlighted by the fact that the E-box elements located in the tyrosinase, TRP-1, TRP-2, and QNR-71 promoters without exception possess a 5' flanking T residue which is entirely conserved between species as diverse as man and turtle. The ability of Mi to discriminate between different E-box motifs provides a mechanism to restrict the repertoire of genes which are likely to be regulated by Mi and provides insight into the ability of bHLH-LZ transcription factors to achieve the specificity required for the precise coordination of transcription during development.
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PMID:Targeting the microphthalmia basic helix-loop-helix-leucine zipper transcription factor to a subset of E-box elements in vitro and in vivo. 981 81

It was previously reported that telomere homologue oligonucleotides (T-oligos) can induce a variety of cellular responses in skin including increased melanogenesis. To assess the effects of T-oligos on hair pigmentation, we administered thymidine dinucleotide (pTT), one-third of the TTAGGG telomere repeat sequence, intradermally at distinct time points of the depilation-induced hair cycle in C3H/HeJ mice. Penetration of T-oligos into the hair follicle (HF) was monitored by using FITC-labelled pTT and confocal microscopy. pTT treatment on days 1-5 after depilation, during early anagen, did not significantly alter the number and proliferation of melanocytes (Trp-2-positive cells), compared with vehicle-treated controls. However, pTT treatment on days 5-12 after depilation, during mid- to late anagen, resulted in the formation of darker hairs, that showed a significantly increased eumelanin/total melanin ratio in their sub-apical agouti band region, compared with vehicle-treated controls (P < 0.05). By RT-PCR and western blot, full thickness skin of pTT-treated mice showed increases in Trp-1, Trp-2 and tyrosinase mRNA and protein levels, compared with control mice. Western blot analyses of two receptors that positively regulate eumelanogenesis, melanocortin type 1 receptor (MC-1R) and kit, showed increased expression of MC-1R protein in pTT-treated versus control skin, while the levels of c-kit receptor remained unchanged. These data demonstrate that pTT treatment increases eumelanogenesis in HFs, associated with increased tyrosinase, TRP-1 and MC-1R expression. These data also raise the possibility of using T-oligos to modulate hair pigmentation.
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PMID:Oligonucleotide treatment increases eumelanogenesis, hair pigmentation and melanocortin-1 receptor expression in the hair follicle. 1762 94

In previous work we described a novel culture technique using a cholera toxin and PMA-free medium (Mel-mix) for obtaining pure melanocyte cultures from human adult epidermis. In Mel-mix medium the cultured melanocytes are bipolar, unpigmented and highly proliferative. Further characterization of the cultured melanocytes revealed the disappearance of c-Kit and TRP-1 and induction of nestin expression, indicating that melanocytes dedifferentiated in this in vitro culture. Cholera toxin and PMA were able to induce c-Kit and TRP-1 protein expressions in the cells, reversing dedifferentiation. TRP-1 mRNA expression was induced in dedifferentiated melanocytes by UV-B irradiated keratinocyte supernatants, however direct UV-B irradiation of the cells resulted in further decrease of TRP-1 mRNA expression. These dedifferentiated, easily accessible cultured melanocytes provide a good model for studying melanocyte differentiation and possibly transdifferentiation. Because melanocytes in Mel-mix medium can be cultured with human serum as the only supplement, this culture system is also suitable for autologous cell transplantation.
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PMID:In vitro dedifferentiation of melanocytes from adult epidermis. 2138 48