Evidence map›Paper›PMID 22069323›Full record

ArticleThe Journal of biological chemistry2011

Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobial peptide LL-37 in human mast cells: resistance to receptor phosphorylation, desensitization, and internalization.

Hariharan Subramanian, Kshitij Gupta, Qiang Guo, Ryan Price, Hydar Ali

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
7.1field-weighted citation impact, top 2% of its field
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

134 citing papers in PubMed, 229 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Direct protamine activation of human mast cells is MRGPRX2-dependent and is modulated by heparin.The Journal of pharmacology and experimental therapeutics · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Modulation of Mast Cell Activation via MRGPRX2 by Natural Oat Extract.International journal of molecular sciences · 2025
    Article
  12. Therapeutic effect of an MRGPRX2/MRGPRB2 antagonist on LL-37-induced rosacea-like inflammation in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
  13. Mutations ofThe journal of allergy and clinical immunology. Global · 2025
    Review
  14. Article
  15. Article
  16. Review
  17. Antimicrobial Peptide Signaling in Skin Diseases.JID innovations : skin science from molecules to population health · 2025
    Review
  18. Article
  19. Beyond the classic players: Mas-related G protein-coupled receptor member X2 role in pruritus and skin diseases.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025
    Review
  20. Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review

74 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

5 authors at 1 institution in 1 country.

Hariharan SubramanianDepartment of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6030, USA.
Kshitij Gupta
Qiang Guo
Ryan Price
Hydar Ali
University of Pennsylvania · US

Funding

G Protein Coupled Receptor Signaling in Mast CellsR01HL085774 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ALI, HYDAR · 2008 to 2011
$1.6M
NHLBI NIH HHS HL085774NHLBI NIH HHS R01 HL085774
6 · The paper itself

Abstract

Human LL-37 is a multifunctional antimicrobial peptide that promotes inflammation, angiogenesis, wound healing, and tumor metastasis. Most effects of LL-37 are mediated via the activation of the cell surface G protein-coupled receptor FPR2 on leukocytes and endothelial cells. Although LL-37 induces chemotaxis, degranulation, and chemokine production in mast cells, the receptor involved and the mechanism of its regulation remain unknown. MrgX2 is a member of Mas-related genes that is primarily expressed in human dorsal root ganglia and mast cells. We found that a human mast cell line LAD2 and CD34(+) cell-derived primary mast cells, which natively express MrgX2, responded to LL-37 for sustained Ca(2+) mobilization and substantial degranulation. However, an immature human mast cell line, HMC-1, that lacks functional MrgX2 did not respond to LL-37. shRNA-mediated knockdown of MrgX2 in LAD2 mast cell line and primary CD34(+) cell-derived mast cells caused a substantial reduction in LL-37-induced degranulation. Furthermore, mast cell lines stably expressing MrgX2 responded to LL-37 for chemotaxis, degranulation, and CCL4 production. Surprisingly, MrgX2 was resistant to LL-37-induced phosphorylation, desensitization, and internalization. In addition, shRNA-mediated knockdown of the G protein-coupled receptor kinases (GRK2 and GRK3) had no effect on LL-37-induced mast cell degranulation. This study identified MrgX2 as a novel G protein-coupled receptor for the antibacterial peptide LL-37 and demonstrated that unlike most G protein-coupled receptors it is resistant to agonist-induced receptor phosphorylation, desensitization, and internalization.

Indexed as

Antimicrobial Cationic PeptidesCalciumCalcium SignalingCathelicidinsCell DegranulationCell LineGene Knockdown TechniquesHumansMast CellsNerve Tissue ProteinsPhosphorylationReceptors, G-Protein-CoupledReceptors, NeuropeptideAntimicrobial Cationic PeptidesCalciumCathelicidinsMRGPRX2 protein, humanNerve Tissue ProteinsReceptors, G-Protein-CoupledReceptors, Neuropeptide

Identifiers

PMID22069323
PMCPMC3247983
OpenAlexW1997746126

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.