Expression of the human melanocortin-2 receptor in different eukaryotic cells

Rached, Mohamed; Mourabit, Haquima El; Buronfosse, A.; Blondet, Antonine; Naville, Danielle; Bégeot, Martine; Penhoat, Armelle

doi:10.1016/j.peptides.2004.11.037

Cited by 33 publications

(15 citation statements)

References 29 publications

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“…2). There was no detectable cAMP response to ACTH when cells were transfected with no receptor or with MC2 receptor alone, consistent with the absence of MC2 receptor and MRAP in these cells (3,18). With free MC2 receptor plus MRAP and with fusion protein, maximal cAMP reporter gene responses were obtained when surface receptor levels were far below maximal.…”

Section: D-f)supporting

confidence: 59%

Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane

Malik

Dolan

Maben

et al. 2015

Journal of Biological Chemistry

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Background:Signaling by G protein-coupled melanocortin-2 receptors requires MRAP, a transmembrane accessory protein that forms antiparallel homodimers. Results: Mutational analysis of MRAP-MRAP-receptor fusion proteins established that MRAP oriented with an extracellular amino terminus is essential. Conclusion: MRAP acts on the outside of the cell in the ACTH-MRAP-MRAP-receptor signaling complex. Significance: The results provide insight into molecular mechanisms of GPCR accessory proteins.

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Section: D-f)supporting

confidence: 59%

Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane

Malik

Dolan

Maben

et al. 2015

Journal of Biological Chemistry

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“…In this regard, a series of studies verified that mammalian MC2R orthologs could not be functionally expressed in non-adrenal-derived cell lines or cells that did not express a MCR (Rached et al 2005, Forti et al 2006, Kilianova et al 2006, Roy et al 2007. In these studies, the MC2R ortholog never appeared to leave the endoplasmic reticulum.…”

Section: Journal Of Molecular Endocrinologymentioning

confidence: 99%

MOLECULAR EVOLUTION OF GPCRS: Melanocortin/melanocortin receptors

Dores¹,

Londraville²,

Prokop³

et al. 2014

Journal of Molecular Endocrinology

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The melanocortin receptors (MCRs) are a family of G protein-coupled receptors that are activated by melanocortin ligands derived from the proprotein, proopiomelanocortin (POMC). During the radiation of the gnathostomes, the five receptors have become functionally segregated (i.e. melanocortin 1 receptor (MC1R), pigmentation regulation; MC2R, glucocorticoid synthesis; MC3R and MC4R, energy homeostasis; and MC5R, exocrine gland physiology). A focus of this review is the role that ligand selectivity plays in the hypothalamus/pituitary/adrenal-interrenal (HPA-I) axis of teleosts and tetrapods as a result of the exclusive ligand selectivity of MC2R for the ligand ACTH. A second focal point of this review is the roles that the accessory proteins melanocortin 2 receptor accessory protein 1 (MRAP1) and MRAP2 are playing in, respectively, the HPA-I axis (MC2R) and the regulation of energy homeostasis by neurons in the hypothalamus (MC4R) of teleosts and tetrapods. In addition, observations are presented on trends in the ligand selectivity parameters of cartilaginous fish, teleost, and tetrapod MC1R, MC3R, MC4R, and MC5R paralogs, and the modeling of the HFRW motif of ACTH(1-24) when compared with a-MSH. The radiation of the MCRs during the evolution of the gnathostomes provides examples of how the physiology of endocrine and neuronal circuits can be shaped by ligand selectivity, the intersession of reverse agonists (agouti-related peptides (AGRPs)), and interactions with accessory proteins (MRAPs).

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“…While the gnathostome MC1R, MC3R, MC4R, and MC5R paralogs can be functionally expressed in mammalian cells lines such as Chinese hamster ovary cells (CHO) or human embryonic kidney cells (HEK-293) (Klovins et al 2004a,b, Ling et al 2004, mammalian MC2R orthologs (Noon et al 2002, Rached et al 2005 as well as teleost (Klovins et al 2004a, Agulleiro et al 2010, amphibian (Liang et al 2011), reptilian (Davis et al 2013), and avian (Ling et al 2004, Barlock et al 2014) MC2R …”

Section: Ligand Selectivity Of Mcrsmentioning

confidence: 99%

“…However, there is a subpopulation of patients that have no point mutations in the MC2R gene, yet are incapable of responding to ACTH. This observation coupled with the realization that mammalian MC2R orthologs could not be functionally expressed in many nonadrenal mammalian cell lines (Noon et al 2002, Rached et al 2005 led to the discovery of the accessory protein MRAP1 (Metherell et al 2005), and later to the discovery of its paralog, MRAP2 (Chan et al 2009). …”

Section: T126 Thematic Reviewmentioning

confidence: 99%

60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides

Dores

Liang

Davis

et al. 2016

Journal of Molecular Endocrinology

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The evolution of the melanocortin receptors (MCRs) is linked to the evolution of adrenocorticotrophic hormone (ACTH), the melanocyte-stimulating hormones (MSHs), and their common precursor pro-opiomelanocortin (POMC). The origin of the MCRs and POMC appears to be grounded in the early radiation of the ancestral protochordates. During the genome duplications that have occurred during the evolution of the chordates, the organization plan for POMC was established, and features that have been retained include, the high conservation of the amino acid sequences of α-MSH and ACTH, and the presence of the HFRW MCR activation motif in all of the melanocortin peptides (i.e. ACTH, α-MSH, β-MSH, γ-MSH, and δ-MSH). For the MCRs, the chordate genome duplication events resulted in the proliferation of paralogous receptor genes, and a divergence in ligand selectivity. While most gnathostome MCRs can be activated by either ACTH or the MSHs, teleost and tetrapod MC2R orthologs can only be activated by ACTH. The appearance of the accessory protein, MRAP1, paralleled the emergence of teleost and tetrapods MC2R ligand selectivity, and the dependence of these orthologs on MRAP1 for trafficking to the plasma membrane. The accessory protein, MRAP2, does not affect MC2R ligand selectivity, but does influence the functionality of MC4R orthologs. In this regard, the roles that these accessory proteins may play in the physiology of the five MCRs (i.e. MC1R, MC2R, MC3R, MC4R, and MC5R) are discussed.

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Expression of the human melanocortin-2 receptor in different eukaryotic cells

Cited by 33 publications

References 29 publications

Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane

Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane

MOLECULAR EVOLUTION OF GPCRS: Melanocortin/melanocortin receptors

60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides

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