Thr40 and Met122 are new partial loss‐of‐function natural mutations of the human melanocortin 1 receptor

FEBS Letters

Sánchez, Jesús¹  Garcı́a-Borrón, José Carlos¹  Germer, Silke¹  Jiménez-Cervantes, Celia¹  Sánchez, Concepción Olivares¹  González, Petra¹ 

[1] Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Apto 4021, 30100 Espinardo, Murcia, Spain

关键词: Melanocortin 1 receptor;    Melanogenesis;    Melanocyte;    Skin type;    G protein-coupled receptor;    cAMP;    AS-PCR;    allele-specific polymerase chain reaction;    GPCR;    G protein-coupled receptor;    MC1R;    melanocortin 1 receptor;    α-MSH;    α-melanocyte stimulating hormone;    NDP-MSH;    [Nle4;    D-Phe7]-α-melanocyte stimulating hormone;    TM;    transmembrane;   

DOI  :  10.1016/S0014-5793(01)03025-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Activation by melanocortins of the melanocortin 1 receptor (MC1R), expressed in epidermal melanocytes, stimulates melanogenesis. Human MC1R gene loss-of-function mutations are associated with fair skin, poor tanning and increased skin cancer risk. We identified two natural alleles: Ile40Thr, probably associated with skin types I–II, and Val122Met. Val122Met bound [¹²⁵I][Nle⁴, D-Phe⁷]-α-melanocyte stimulating hormone with lower affinity than the wild-type. Dose–response curves of cAMP accumulation were right-shifted for both forms. The Val122Met form failed to achieve maximal cAMP responses comparable to the wild-type or Ile40Thr receptors. Thus, the Ile40Thr and Val122Met variants are partial loss-of-function natural mutations of MC1R.

【 授权许可】

Unknown