Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes
Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes
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DOI：
10.1111/j.1600-0625.2011.01293.x
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发表时间：
2011-08-01
影响因子：
3.6
通讯作者：
Sturm, Richard A.
中科院分区：
文献类型：
--
作者：
Ainger, Stephen A.;Wong, Shu S.;Sturm, Richard A.
使用黑素细胞和角质形成细胞的共培养系统来检查与野生型（WT）细胞相比，在低渗透'r'纯合子和'R/+'杂合子MC 1 R变体等位基因表达细胞中的树突和多巴色素互变异构酶（DCT）反应。V60 L-/-纯合子r变异细胞显示出与WT MC 1 R株相似的配体应答，而V92 M（-/-）纯合子r变异细胞通常显示出比WT细胞具有更大的树突度并且表达更高的DCT，甚至在基础水平。R151 C +/-杂合子细胞对WT细胞表现出类似的反应，而R160 W +/-和D294 H +/-变体细胞对NDP-MSH的反应降低，但对毛喉素处理仍具有活性cAMP反应。这些反应与这些等位基因对MC 1 R WT等位基因的显性负效应一致，这一效应先前已在遗传学和生物化学上得到证实。
A co-culture system of melanocytic cells and keratinocytes was used to examine dendricity and dopachrome tautomerase (DCT) responses in low penetrant 'r' homozygote and 'R/+' heterozygote MC1R variant allele expressing cells compared to that of wild-type (WT) cells. The V60L-/- homozygote r variant cells showed similar responses to ligand as WT MC1R strains, while V92M(-/-) homozygote r variant cells were generally shown to have greater dendricity and express higher DCT than the WT cells, even at basal levels. The R151C+/- heterozygote cells showed similar responses to WT cells, while the R160W+/- and D294H+/- variant cells were reduced in their responses to NDP-MSH, but still had an active cAMP response with forskolin treatment. These responses are consistent with the dominant negative effect of these alleles on the MC1R WT allele that has previously been demonstrated genetically and biochemically.