2014
DOI: 10.1530/jme-14-0169
|View full text |Cite
|
Sign up to set email alerts
|

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

Abstract: 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 rec… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
2
1

Citation Types

0
8
0

Year Published

2015
2015
2023
2023

Publication Types

Select...
7
1

Relationship

0
8

Authors

Journals

citations
Cited by 10 publications
(8 citation statements)
references
References 41 publications
(43 reference statements)
0
8
0
Order By: Relevance
“…This substitution blocked the ACTH activation of the mutated hMC2R (Chung et al 2008). Studies by Fridmanis et al (2010Fridmanis et al ( , 2014) also point to the importance of extracellular loop 2 for the activation of hMC2R.…”
Section: ) (B)mentioning
confidence: 87%
“…This substitution blocked the ACTH activation of the mutated hMC2R (Chung et al 2008). Studies by Fridmanis et al (2010Fridmanis et al ( , 2014) also point to the importance of extracellular loop 2 for the activation of hMC2R.…”
Section: ) (B)mentioning
confidence: 87%
“…Unfortunately, the mammalian and elephant shark receptors are sufficiently different that a basis for MRAP dependence cannot be deduced readily from their sequences (11). Several groups have gener- ated MC2/MC4 receptor chimeras in an effort to pinpoint the differences that account for MRAP dependence (25)(26)(27)(28). This approach has not provided any simple answers either, but the data are consistent with involvement of the receptor amino terminus, outer regions of transmembrane helices 2 and 3, and the second extracellular loop, which could interact with the N out MRAP partner, as well as receptor transmembrane domains.…”
Section: Discussionmentioning
confidence: 99%
“…Neither corresponding domains in hMC2R (trafficking or activation) had been identified prior to 2010. Initial attempts at resolving these issues have used a chimeric receptor paradigm [30,31], and collectively these studies point to a role for TM4 in trafficking of hMC2R. In addition, the results from both studies could be explained by assuming that formation of the heterodimer between MRAP1 and MC2R results in a conformation change in the receptor which places the R/KKRR binding site (presumably EC2) in the proper conformation for the activation process to begin.…”
Section: Discussionmentioning
confidence: 99%