Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs), which constitute the largest family of membrane proteins, mediate responses to diverse physiological stimuli. The presence of melanocortin 2 receptors (MC2Rs) on the plasma membrane requires the presence of either MC2R accessory protein (MRAP) or MRAP2, which are homologous accessory proteins. Here, we show that, whereas MRAP was essential for activation of MC2R signaling, MRAP2 was an endogenous inhibitor that competed with MRAP for binding to MC2R and decreased the potency of adrenocorticotropic hormone (ACTH), the endogenous agonist for MC2Rs, in stimulating the production of adenosine 3',5'-monophosphate (cAMP). ACTH bound with high affinity to MC2Rs in the presence of MRAP, but not MRAP2. The ability of MRAP and MRAP2 to influence ligand-binding affinity was specific to MC2R, because these proteins had little effect on the binding of NDP-alpha-melanocyte-stimulating hormone to MC4R or on its stimulation of cAMP responses. These results demonstrate that the balance of stimulatory and inhibitory accessory proteins can control the sensitivity of a GPCR to its natural agonist.
Pharmacology, Toxicology and Pharmaceutical Science
2
3%
Other
4
7%
Unknown
13
22%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 July 2018.
All research outputs
#7,454,951
of 22,792,160 outputs
Outputs from Science Signaling
#1,858
of 3,155 outputs
Outputs of similar age
#34,549
of 94,882 outputs
Outputs of similar age from Science Signaling
#8
of 22 outputs
Altmetric has tracked 22,792,160 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,155 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.7. This one is in the 38th percentile – i.e., 38% of its peers scored the same or lower than it.
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We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
