Affiliation:
1. Department of Biological Sciences, University of Denver, Denver, Colorado 80210
Abstract
Abstract
Phylogenetic analyses indicate that the genome of the cartilaginous fish, Callorhynchus milii (elephant shark), encodes a melanocortin-2 receptor (MC2R) ortholog. Expression of the elephant shark mc2r cDNA in Chinese hamster ovary (CHO) cells revealed that trafficking to the plasma membrane and functional activation of the receptor do not require coexpression with an exogenous melanocortin receptor-2 accessory protein (mrap) cDNA. Ligand selectivity studies indicated that elephant shark MC2R-transfected CHO cells produced cAMP in a dose-dependent manner when stimulated with either human ACTH (1–24) or [Nle4, d-Phe7]-MSH. Furthermore, the order of ligand selectivity when elephant shark MC2R-transfected CHO cells were stimulated with cartilaginous fish melanocortins was as follows: ACTH (1–25) = γ-MSH = δ-MSH > αMSH = β-MSH. Elephant shark MC2R is the first vertebrate MC2R ortholog to be analyzed that does not require melanocortin receptor-2 accessory protein 1 for functional activation. In addition, elephant MC2R is currently the only MC2R ortholog that can be activated by either ACTH- or MSH-sized ligands. Hence, it would appear that MC2R dependence on melanocortin receptor-2 accessory protein 1 for functional activation and the exclusive selectivity of this melanocortin receptor for ACTH are features that emerged after the divergence of the ancestral cartilaginous fishes and the ancestral bony fishes more than 400 million years ago.
Cited by
39 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献