Department of Life Sciences, Anglia Ruskin University, OPT 028, East Road, Cambridge CB1 1PT, UK.
University of East Anglia, UK.
FEBS Lett. 2014 Jun 27;588(14):2335-43. doi: 10.1016/j.febslet.2014.05.032. Epub 2014 May 28.
The melanocortin-1 receptor (MC1R) is a key regulator of mammalian pigmentation. Melanism in the grey squirrel is associated with an eight amino acid deletion in the mutant melanocortin-1 receptor with 24 base pair deletion (MC1RΔ24) variant. We demonstrate that the MC1RΔ24 exhibits a higher basal activity than the wildtype MC1R (MC1R-wt). We demonstrate that agouti signalling protein (ASIP) is an inverse agonist to the MC1R-wt but is an agonist to the MC1RΔ24. We conclude that the deletion in the MC1RΔ24 leads to a receptor with a high basal activity which is further activated by ASIP. This is the first report of ASIP acting as an agonist to MC1R.
黑素皮质素 1 受体 (MC1R) 是哺乳动物色素沉着的关键调节剂。灰色松鼠的黑化与突变黑素皮质素 1 受体中 24 个碱基缺失 (MC1RΔ24) 变异的八个氨基酸缺失有关。我们证明 MC1RΔ24 比野生型 MC1R (MC1R-wt) 具有更高的基础活性。我们证明刺鼠相关蛋白 (ASIP) 是 MC1R-wt 的反向激动剂，但对 MC1RΔ24 是激动剂。我们得出结论，MC1RΔ24 中的缺失导致受体具有高基础活性，ASIP 进一步激活该受体。这是 ASIP 作为 MC1R 激动剂发挥作用的第一个报道。
