鉴定和功能分析的小说变异人类黑色素瘤患者中发现的肾上腺受体。
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佩雷斯·奥利瓦AB Fernendez LP, Detorre C, Herraiz C, Martinez-Escribano是的,贝尼特斯J, Lozano前线是的,Garcia-Borron JC, Jimenez-Cervantes C、G里巴斯
鉴定和功能分析的小说变异人类黑色素瘤患者中发现的肾上腺受体。
哼Mutat。2009; 30(5): 811 - 22所示。doi: 10.1002 / humu.20971。
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19338054 (在PubMed]
- 文摘
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Gs protein-coupled肾上腺受体,受体表达在表皮黑色素细胞,皮肤色素沉着和凸版照相的主要决定因素,黑色素瘤风险的一个重要因素。受体活化刺激合成黑色,强烈的光保护真黑素色素。几个MC1R等位基因与红色的头发,白皙的皮肤,增加了对紫外线的敏感性,增加皮肤癌的风险。黑素皮质素受体基因是高度多态,但只有少数天然等位基因功能的特点,这就不利于建立准确的信号特性突变等位基因之间的相关性和皮肤的表型定义。我们报告的功能描述六个MC1R等位基因中发现西班牙的黑色素瘤患者。两种变体(c。152 t > C、p。Val51Ala和c。865 t > C p.Cys289Arg)从未被描述,和其他人(C。112 g > A, p.Val38Met;c。122 c > T, p.Ser41Phe; c.383T>C, p.Met128Thr; and c.842A>G, p.Asn281Ser) have not been analyzed for function. p.Asn281Ser corresponds to a functionally silent polymorphism. The other mutations are associated with varying degrees of loss of function (LOF), from moderate decreases in coupling to the cAMP pathway (p.Val38Met and p.Val51Ala) to nearly complete absence of functional coupling (p.Ser41Phe, p.Met128Thr, and p.Cys289Arg). The LOF p.Met128Thr and p.Cys289Arg mutants are trafficked to the cell surface, but are unable to bind agonists efficiently. Conversely, LOF of p.Val38Met, p.Ser41Phe, and p.Val51Ala is due to reduced cell surface expression as a consequence of retention in the endoplasmic reticulum (ER). Therefore, LOF of MC1R alleles is frequently associated with aberrant forward trafficking and accumulation within the ER or with inability to bind properly the activatory ligand.