Replacement of short segments within transmembrane domains of MC2R disrupts retention signal

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: id:"swepub:oai:DiVA.org:uu-238743" > Replacement of shor...

1 of 1
Previous record
Next record
To hitlist

Details
MARC

Fridmanis, DavidsUppsala universitet,Funktionell farmakologi (author)

Replacement of short segments within transmembrane domains of MC2R disrupts retention signal

Article/chapterEnglish2014

Publisher, publication year, extent ...

2014
printrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-238743
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-238743URI
https://doi.org/10.1530/JME-14-0169DOI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

The proteolysis of the pro-opiomelanocortin precursor results in the formation of melanocortins (MCs), a group of peptides that share the conserved -H-F-R-W- sequence, which acts as a pharmacophore for five subtypes of MC receptors (MCRs). MC type 2 receptor (MC2R; also known as ACTHR) is the most specialized of all the MCRs. It is predominantly expressed in the adrenal cortex and specifically binds ACTH. Unlike other MCRs, it requires melanocortin receptor accessory protein 1 (MRAP) for formation of active receptor and for its transport to the cell membrane. The molecular mechanisms underlying this specificity remain poorly understood. In this study, we used directed mutagenesis to investigate the role of various short MC2R sequence segments in receptor membrane trafficking and specific activation upon stimulation with ligands. The strategy of the study was to replace two to five amino acid residues within one MC2R segment with the corresponding residues of MC4R. In total, 20 recombinant receptors C-terminally fused to enhanced green fluorescent protein were generated and their membrane trafficking efficiencies and cAMP response upon stimulation with α-MSH and ACTH(1-24) were estimated during their stand-alone expression and coexpression with MRAP. Our results indicate that both the motif that determines the ligand-recognition specificity and the intracellular retention signal are formed by a specific extracellular structure, which is supported by the correct alignment of the transmembrane domains. Our results also indicate that the aromatic-residue-rich segment of the second extracellular loop is involved in the effects mediated by the second ACTH pharmacophore (-K-K-R-R-).

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

Petrovska, Ramona (author)
Pjanova, Dace (author)
Schiöth, Helgi B.Uppsala universitet,Funktionell farmakologi(Swepub:uu)helgschi (author)
Klovins, JanisUppsala universitet,Funktionell farmakologi (author)
Uppsala universitetFunktionell farmakologi (creator_code:org_t)

Related titles

In:Journal of Molecular Endocrinology53:2, s. 201-2150952-50411479-6813

Internet link

Find in a library

Journal of Molecular Endocrinology (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Fridmanis, David ...; Petrovska, Ramon ...; Pjanova, Dace; Schiöth, Helgi B ...; Klovins, Janis

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

Articles in the publication: Journal of Molec ...

By the university: Uppsala University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se