The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW

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The orphan G protein-coupled receptor GPR139 is activated by the peptides : Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW. / Jensen, Anne Cathrine Nøhr; Shehata, Mohamed A; Hauser, Alexander S; Isberg, Vignir; Mokrosinski, Jacek; Farooqi, I Sadaf; Pedersen, Daniel Sejer; Gloriam, David E; Bräuner-Osborne, Hans.

In: Neurochemistry International, Vol. 102, 01.01.2017, p. 105-113.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jensen, ACN, Shehata, MA, Hauser, AS, Isberg, V, Mokrosinski, J, Farooqi, IS, Pedersen, DS, Gloriam, DE & Bräuner-Osborne, H 2017, 'The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW', Neurochemistry International, vol. 102, pp. 105-113. https://doi.org/10.1016/j.neuint.2016.11.012

APA

Jensen, A. C. N., Shehata, M. A., Hauser, A. S., Isberg, V., Mokrosinski, J., Farooqi, I. S., ... Bräuner-Osborne, H. (2017). The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW. Neurochemistry International, 102, 105-113. https://doi.org/10.1016/j.neuint.2016.11.012

Vancouver

Jensen ACN, Shehata MA, Hauser AS, Isberg V, Mokrosinski J, Farooqi IS et al. The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW. Neurochemistry International. 2017 Jan 1;102:105-113. https://doi.org/10.1016/j.neuint.2016.11.012

Author

Jensen, Anne Cathrine Nøhr ; Shehata, Mohamed A ; Hauser, Alexander S ; Isberg, Vignir ; Mokrosinski, Jacek ; Farooqi, I Sadaf ; Pedersen, Daniel Sejer ; Gloriam, David E ; Bräuner-Osborne, Hans. / The orphan G protein-coupled receptor GPR139 is activated by the peptides : Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW. In: Neurochemistry International. 2017 ; Vol. 102. pp. 105-113.

Bibtex

@article{3594e2cb171b405880c5f3be0732b47a,
title = "The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW",
abstract = "GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139. Based on the chemogenomics principle {"}similar targets bind similar ligands{"}, we tested three known endogenous melanocortin 4 receptor agonists; adrenocorticotropic hormone (ACTH) and α- and β-melanocyte stimulating hormone (α-MSH and β-MSH) on CHO-k1 cells stably expressing the human GPR139 in a Fluo-4 Ca(2+)-assay. All three peptides, as well as their conserved core motif HFRW, were found to activate GPR139 in the low μM range. Moreover, we found that peptides consisting of nine or ten N-terminal residues of α-MSH activate GPR139 in the submicromolar range. α-MSH1-9 was found to correspond to the product of a predicted cleavage site in the pre-pro-protein pro-opiomelanocortin (POMC). Our results demonstrate that GPR139 is a peptide receptor, activated by ACTH, α-MSH, β-MSH, the conserved core motif HFRW as well as a potential endogenous peptide α-MSH1-9. Further studies are needed to determine the functional relevance of GPR139 mediated signaling by these peptides.",
keywords = "The Faculty of Health and Medical Sciences, selected",
author = "Jensen, {Anne Cathrine N{\o}hr} and Shehata, {Mohamed A} and Hauser, {Alexander S} and Vignir Isberg and Jacek Mokrosinski and Farooqi, {I Sadaf} and Pedersen, {Daniel Sejer} and Gloriam, {David E} and Hans Br{\"a}uner-Osborne",
note = "Copyright {\^A}{\circledC} 2016. Published by Elsevier Ltd.",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.neuint.2016.11.012",
language = "English",
volume = "102",
pages = "105--113",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - The orphan G protein-coupled receptor GPR139 is activated by the peptides

T2 - Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW

AU - Jensen, Anne Cathrine Nøhr

AU - Shehata, Mohamed A

AU - Hauser, Alexander S

AU - Isberg, Vignir

AU - Mokrosinski, Jacek

AU - Farooqi, I Sadaf

AU - Pedersen, Daniel Sejer

AU - Gloriam, David E

AU - Bräuner-Osborne, Hans

N1 - Copyright © 2016. Published by Elsevier Ltd.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139. Based on the chemogenomics principle "similar targets bind similar ligands", we tested three known endogenous melanocortin 4 receptor agonists; adrenocorticotropic hormone (ACTH) and α- and β-melanocyte stimulating hormone (α-MSH and β-MSH) on CHO-k1 cells stably expressing the human GPR139 in a Fluo-4 Ca(2+)-assay. All three peptides, as well as their conserved core motif HFRW, were found to activate GPR139 in the low μM range. Moreover, we found that peptides consisting of nine or ten N-terminal residues of α-MSH activate GPR139 in the submicromolar range. α-MSH1-9 was found to correspond to the product of a predicted cleavage site in the pre-pro-protein pro-opiomelanocortin (POMC). Our results demonstrate that GPR139 is a peptide receptor, activated by ACTH, α-MSH, β-MSH, the conserved core motif HFRW as well as a potential endogenous peptide α-MSH1-9. Further studies are needed to determine the functional relevance of GPR139 mediated signaling by these peptides.

AB - GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139. Based on the chemogenomics principle "similar targets bind similar ligands", we tested three known endogenous melanocortin 4 receptor agonists; adrenocorticotropic hormone (ACTH) and α- and β-melanocyte stimulating hormone (α-MSH and β-MSH) on CHO-k1 cells stably expressing the human GPR139 in a Fluo-4 Ca(2+)-assay. All three peptides, as well as their conserved core motif HFRW, were found to activate GPR139 in the low μM range. Moreover, we found that peptides consisting of nine or ten N-terminal residues of α-MSH activate GPR139 in the submicromolar range. α-MSH1-9 was found to correspond to the product of a predicted cleavage site in the pre-pro-protein pro-opiomelanocortin (POMC). Our results demonstrate that GPR139 is a peptide receptor, activated by ACTH, α-MSH, β-MSH, the conserved core motif HFRW as well as a potential endogenous peptide α-MSH1-9. Further studies are needed to determine the functional relevance of GPR139 mediated signaling by these peptides.

KW - The Faculty of Health and Medical Sciences

KW - selected

U2 - 10.1016/j.neuint.2016.11.012

DO - 10.1016/j.neuint.2016.11.012

M3 - Journal article

VL - 102

SP - 105

EP - 113

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

ER -

ID: 169737945