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Study · Not a test of the peptide alone · 2018

4 results

Glucose-regulated protein 78 binds to and regulates the melanocortin-4 receptor.

Yoon YR, Lee TG, Choi MH, Shin SW, Ko YG, Rhyu IJ, Kim DH, Seong JK, Baik JH

Experimental & molecular medicine12 Sept 2018Cited by 11 (Europe PMC)

PMID30209265 (opens in a new tab)PMCIDPMC6135830 (opens in a new tab)DOI10.1038/s12276-018-0144-8 (opens in a new tab)PepBankPUB-30209265
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Summary

The melanocortin-4 receptor (MC4R) belongs to the G protein-coupled receptor (GPCR) family and plays an essential role in the control of energy homeostasis. Here, we identified a novel MC4R-interacting protein, glucose-regulated protein 78 (GRP78), from a pulldown assay using hypothalamic protein extracts and the third intracellular loop of MC4R. We found that MC4R interacted with GRP78 in both the cytosol and at the cell surface and that this interaction increased when MC4R was internalized in the presence of the agonist melanotan-II (MTII). Downregulation of GRP78 using a short interfering RNA approach attenuated MTII-mediated receptor internalization. Reduction in GRP78 expression during tunicamycin-induced endoplasmic reticulum stress also suppressed MTII-mediated internalization of MC4R and cAMP-mediated transcriptional activity. Furthermore, lentiviral-mediated short hairpin RNA knockdown of endogenous GRP78 in the paraventricular nucleus (PVN) of the hypothalamus resulted in an increase in body weight in mice fed a high-fat diet. These results suggest that GRP78 in the PVN binds to MC4R and may have a chaperone-like role in the regulation of MC4R trafficking and signaling.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone4

In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Melanotan II.

  1. 01LabNot a test of Melanotan II aloneIn vitro (cells)Mechanism

    The interaction between MC4R and GRP78 increased when MC4R was internalized in the presence of the agonist MTII.

    In plain wordsIn cells, MC4R bound GRP78 more when MC4R was taken into the cell after MTII.

    Peptide
    Melanotan II
    Outcome
    IncreaseMC4R-GRP78 interaction during MTII-induced internalization
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Metabolic and weight

    Source sentences

    Summary
    We found that MC4R interacted with GRP78 in both the cytosol and at the cell surface and that this interaction increased when MC4R was internalized in the presence of the agonist melanotan-II (MTII).

    In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.

  2. 02LabNot a test of Melanotan II aloneIn vitro (cells)Mechanism

    Downregulating GRP78 with short interfering RNA attenuated MTII-mediated MC4R internalization.

    In plain wordsIn cells, lowering GRP78 reduced how much MC4R was taken into the cell after MTII.

    Peptide
    Melanotan II
    Outcome
    DecreaseMTII-mediated MC4R internalization after GRP78 knockdown
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Metabolic and weight

    Source sentences

    Summary
    Downregulation of GRP78 using a short interfering RNA approach attenuated MTII-mediated receptor internalization.

    In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.

  3. 03LabNot a test of Melanotan II aloneIn vitro (cells)Mechanism

    Reduced GRP78 expression during tunicamycin-induced endoplasmic reticulum stress suppressed MTII-mediated MC4R internalization.

    In plain wordsIn cells under stress, less GRP78 meant less MC4R was taken into the cell after MTII.

    Peptide
    Melanotan II
    Outcome
    DecreaseMTII-mediated MC4R internalization during ER stress
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Metabolic and weight

    Source sentences

    Summary
    Reduction in GRP78 expression during tunicamycin-induced endoplasmic reticulum stress also suppressed MTII-mediated internalization of MC4R

    In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.

  4. 04LabNot a test of Melanotan II aloneIn vitro (cells)Mechanism

    Reduced GRP78 expression during tunicamycin-induced endoplasmic reticulum stress suppressed cAMP-mediated transcriptional activity of MC4R.

    In plain wordsIn cells under stress, less GRP78 meant lower cAMP-driven gene activity.

    Peptide
    Melanotan II
    Outcome
    DecreasecAMP-mediated transcriptional activity during ER stress
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Metabolic and weight

    Source sentences

    Summary
    Reduction in GRP78 expression during tunicamycin-induced endoplasmic reticulum stress also suppressed MTII-mediated internalization of MC4R and cAMP-mediated transcriptional activity.

    In this study, Melanotan II was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Melanotan II.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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