GRK2 differentially regulates FcεRI and MRGPRB2-mediated responses in mast cells

Article Dermatology

Role of MrgprB2 in Rosacea-Like Inflammation in Mice: Modulation by β-Arrestin 2

Saptarshi Roy et al.

Summary: This study found that MRGPRX2 participates in the pathogenesis of rosacea, and beta-arrestin 2 contributes to its development by promoting mast cell chemotaxis and the production of inflammatory mediators.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2022)

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Article Immunology

GRK2 inhibitors, paroxetine and CCG258747, attenuate IgE-mediated anaphylaxis but activate mast cells via MRGPRX2 and MRGPRB2

Monica Thapaliya et al.

Summary: Research has shown that GRK2 inhibitors paroxetine and CCG258747 can effectively modulate MC responses mediated by IgE, reducing allergic reactions and enhancing cutaneous host defense.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Immunology

Inhibition of MRGPRX2 but not FcεRI or MrgprB2-mediated mast cell degranulation by a small molecule inverse receptor agonist

Maram Bawazir et al.

Summary: The MRGPRX2 receptor plays a role in hypersensitivity reactions and cutaneous conditions. The MRGPRX2 agonist C9 has shown potential in modulating MC-mediated disorders.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Dermatology

MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through β-Arrestin and Lack of Correlation with the FcεRI Pathway

Magda Babina et al.

Summary: Codeine activates dermal mast cells through MRGPRX2 as its dominant receptor, with activation displaying individual variability and being subject to desensitization. Codeine-induced activation of MRGPRX2 leads to rapid internalization and E3-arrestin activation, suggesting a potential mechanism for refractoriness. Pre-stimulation with MRGPRX2 agonists results in cross desensitization, indicating a possible strategy to prevent severe pseudoallergic reactions.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2021)

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Article Gastroenterology & Hepatology

Inflamed Ulcerative Colitis Regions Associated With MRGPRX2-Mediated Mast Cell Degranulation and Cell Activation Modules, Defining a New Therapeutic Target

Ernie Chen et al.

Summary: The research reveals that in human UC, inflamed regions are distinguished by MRGPRX2-mediated activation of mast cells, with decreased activation observed with a UC-protective genetic variant. These results provide important clues for the cell modules of UC activation and a new therapeutic target.

GASTROENTEROLOGY (2021)

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Article Cell Biology

MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants

Chalatip Chompunud Na Ayudhya et al.

Summary: The study found that rocuronium induces degranulation in human MCs via the receptor MRGPRX2, indicating a more complex mechanism of perioperative hypersensitivity than previously thought due to differences between MRGPRX2 and MrgprB2, and the lack of enhanced response in cells expressing MRGPRX2 variants.

CELLS (2021)

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Review Cell Biology

Historical Perspective of the G Protein-Coupled Receptor Kinase Family

Jeffrey L. Benovic

Summary: Agonist activation of G protein-coupled receptors leads to sequential interaction with G proteins, GRKs, and arrestins. GRKs play a central role in mediating the switch from G protein to arrestin interaction and controlling processes like receptor desensitization. Early studies on GRK identification and cloning laid the foundation for understanding the structure and function of these enzymes.

CELLS (2021)

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Article Biochemistry & Molecular Biology

Substance P Serves as a Balanced Agonist for MRGPRX2 and a Single Tyrosine Residue Is Required for β-Arrestin Recruitment and Receptor Internalization

Chalatip Chompunud Na Ayudhya et al.

Summary: The neuropeptide substance P activates mast cells through MrgprB2, contributing to neurogenic inflammation and pain in atopic dermatitis. Certain MRGPRX2 agonists lead to beta-arrestin recruitment, revealing a new pathway for receptor internalization and desensitization. The study highlights a tyrosine residue in the highly conserved NPxxY motif of MRGPRX2 that plays a role in both G protein- and beta-arrestin-mediated responses.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Stat5B is required for IgE-Mediated mast cell function in vitro and in vivo

Kasalina N. Kiwanuka et al.

Summary: The lack of Stat5B in mice results in reduced responses to IgE-mediated anaphylaxis and diminished IgE-induced degranulation and cytokine secretion in mast cells. These findings suggest that the Stat5B isoform is crucial for normal mast cell function and may play a role in limiting IgE production in vivo.

CELLULAR IMMUNOLOGY (2021)

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Article Immunology

Murepavadin, a Small Molecule Host Defense Peptide Mimetic, Activates Mast Cells via MRGPRX2 and MrgprB2

Aetas Amponnawarat et al.

Summary: Pseudomonas aeruginosa infections are difficult to treat due to biofilm formation and antibiotic resistance, but a lipidated HDP mimetic called murepavadin has shown antibacterial activity against multi-drug-resistant strains. Murepavadin activates human MCs via MRGPRX2 and murine MCs via MrgprB2, potentially contributing to bacterial clearance and wound healing.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Immunology