The melanocortin-2 receptor of the rainbow trout: Identifying a role for critical positions in transmembrane domain 4, extracellular loop 2, and transmembrane domain 5 in the activation of rainbow trout MC2R

General and Comparative Endocrinology
Liang LiangRobert M Dores

Abstract

The activation of either teleost or tetrapod melanocortin-2 receptor (MC2R) orthologs requires interaction between the HFRW motif and R/KKRRP motif in the primary sequence of ACTH, and two corresponding sites on the melanocortin 2 receptor. While the HFRW contact site on MC2R appears to involve residues in TM2, TM3, and TM6, several studies on human MC2R point to the EC2/TM5 region of MC2R as a possible location for the R/KKRRP contact site. In this study nineteen single-alanine mutants of rainbow trout (rt) MC2R were made beginning at V153 in TM4, at all positions in EC2 (extracellular loop 2), to F175 in TM5. For twelve of these alanine mutants (i.e., V153, G155, C162, D163, T165, V166, I167, H169, F170, H172, V173, L174), alanine substitution did not have a statistically significant effect on activation of the receptor. For four of these alanine mutations (i.e., V157, M158, F161, K168), while the negative shift in ligand sensitivity was statistically significant, the magnitude of the negative shift in activation was fivefold or less. However, for substitution at V159 in TM4 (negative shift in activation: 110 fold), F171 in TM5 (negative shift in activation: 48-fold), and F175 in TM5 (negative shift in activation: 100 fold), ...Continue Reading

References

Oct 28, 1977·Annals of the New York Academy of Sciences·R Schwyzer
May 3, 2005·General and Comparative Endocrinology·Robert M Dores, Stephanie Lecaude
Aug 24, 2005·Biochemistry·Irina D PogozhevaHenry I Mosberg
Nov 2, 2006·Endocrine Reviews·Roger D Cone
Nov 26, 2008·Molecular and Cellular Endocrinology·Patricia M Hinkle, Julien A Sebag
Oct 27, 2009·Molecular Endocrinology·Tom R Webb, Adrian J L Clark
Feb 9, 2010·Molecular and Cellular Endocrinology·Maria Josep AgulleiroJosé Miguel Cerdá-Reverter
Aug 19, 2011·General and Comparative Endocrinology·Liang LiangRobert M Dores
Apr 9, 2014·General and Comparative Endocrinology·Liang LiangRobert M Dores
Apr 10, 2014·General and Comparative Endocrinology·Robert M Dores, Liang Liang
Jan 13, 2015·Molecular and Cellular Endocrinology·Robert M Dores, Yesenia Garcia
Jan 23, 2016·Journal of Molecular Endocrinology·Robert M DoresBogdana Petko

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