Evidence map›Paper›PMID 9450927›Full record

ArticleGenes & development1998

Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo.

M M Ollmann, M L Lamoreux, B D Wilson, G S Barsh

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 232 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects.International journal of molecular sciences · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. An enhancer ofProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  15. Veterinary sciences · 2022
    Article
  16. Article
  17. Differentiating Pigs from Wild Boars Based onAnimals : an open access journal from MDPI · 2021
    Article
  18. Review
  19. Review
  20. Polymorphism of the Melanocortin 1 Receptor (Animals : an open access journal from MDPI · 2020
    Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 4 institutions in 1 country.

M M OllmannDepartment of Pediatrics, and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5428, USA.
M L Lamoreux
B D Wilson
G S Barsh
Howard Hughes Medical Institute · USPediatrics and Genetics · USStanford University · USTexas A&M University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
PATHOGENESIS OF OCULAR ALBINISMR01EY010223 · NEI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ORLOW, SETH J. · 1994 to 2005
$1.9M
GENETICS TRAINING PROGRAM FOR PHD CANDIDATEST32EY007106 · NEI · STANFORD UNIVERSITY · PI BOTSTEIN, DAVID · 1988 to 1999
–
NEI NIH HHS EY07106NEI NIH HHS EY 10223NEI NIH HHS R01 EY010223NEI NIH HHS T32 EY007106NIGMS NIH HHS GM07365NIGMS NIH HHS T32 GM007365
6 · The paper itself

Abstract

Agouti protein and Agouti-related protein (Agrp) are paracrine-signaling molecules that normally regulate pigmentation and body weight, respectively. These proteins antagonize the effects of alpha-melanocyte-stimulating hormone (alpha-MSH) and other melanocortins, and several alternatives have been proposed to explain their biochemical mechanisms of action. We have used a sensitive bioassay based on Xenopus melanophores to characterize pharmacologic properties of recombinant Agouti protein, and have directly measured its cell-surface binding to mammalian cells by use of an epitope-tagged form (HA-Agouti) that retains biologic activity. In melanophores, Agouti protein has no effect in the absence of alpha-MSH, but its action cannot be explained solely by inhibition of alpha-MSH binding. In 293T cells, expression of the Mc1r confers a specific, high-affinity binding site for HA-Agouti. Binding is inhibited by alpha-MSH, or by Agrp, which indicates that alpha-MSH and Agouti protein bind in a mutually exclusive way to the Mc1r, and that the similarity between Agouti protein and Agrp includes their binding sites. The effects of Agouti and the Mc1r in vivo have been examined in a sensitized background provided by the chinchilla (Tyrc-ch) mutation, which uncovers a phenotypic difference between overexpression of Agouti in lethal yellow (Ay/a) mice and loss of Mc1r function in recessive yellow (Mc1re/Mc1re) mice. Double and triple mutant studies indicate that a functional Mc1r is required for the pigmentary effects of Agouti, and suggest that Agouti protein can act as an agonist of the Mc1r in a way that differs from alpha-MSH stimulation. These results resolve questions regarding the biochemical mechanism of Agouti protein action, and provide evidence of a novel signaling mechanism whereby alpha-MSH and Agouti protein or Agrp function as independent ligands that inhibit each other's binding and transduce opposite signals through a single receptor.

Indexed as

Intercellular Signaling Peptides and ProteinsAgouti-Related ProteinAgouti Signaling Proteinalpha-MSHAnimalsEpitopesMelanophoresMiceMice, Inbred C57BLPigmentationProtein BindingProteinsReceptors, CorticotropinReceptors, MelanocortinRecombinant ProteinsXenopusAgouti-Related ProteinAgouti Signaling ProteinAgrp protein, mousealpha-MSHa protein, mouseEpitopesIntercellular Signaling Peptides and ProteinsProteinsReceptors, CorticotropinReceptors, MelanocortinRecombinant Proteins

Identifiers

PMID9450927
PMCPMC316484
OpenAlexW2106052620

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.