ArticleThe Journal of investigative dermatology2014
MAPKAP kinase 2 (MK2)-dependent and -independent models of blister formation in pemphigus vulgaris.
Article in The Journal of investigative dermatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- What protein kinases are crucial for acantholysis and blister formation in pemphigus vulgaris? A systematic review.Journal of cellular physiology · 2022Pooled it
- Desmoglein-driven dynamic signaling in pemphigus vulgaris: a systematic review of pathogenic pathways.NPJ Regenerative medicine · 2025Article
- The impact of signaling pathways on the desmosome ultrastructure in pemphigus.Frontiers in immunology · 2024Article
- Tacrolimus reverses pemphigus vulgaris serum-induced depletion of desmoglein in HaCaT cells via inhibition of heat shock protein 27 phosphorylation.BMC immunology · 2023Article
- Targeting SERCA2 in organotypic epidermis reveals MEK inhibition as a therapeutic strategy for Darier disease.JCI insight · 2023Article
- Mouse models of pemphigus: valuable tools to investigate pathomechanisms and novel therapeutic interventions.Frontiers in immunology · 2023Review
- Pemphigus and Pemphigoid: From Disease Mechanisms to Druggable Pathways.The Journal of investigative dermatology · 2022Review
- Mechanisms Causing Acantholysis in Pemphigus-Lessons from Human Skin.Frontiers in immunology · 2022Review
- Autoantibody-Specific Signalling in Pemphigus.Frontiers in medicine · 2021Review
- Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody-negative pemphigus vulgaris.The Journal of biological chemistry · 2019Article
- Pemphigus: Current and Future Therapeutic Strategies.Frontiers in immunology · 2019Review
- Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model.Frontiers in immunology · 2018Review
- Pemphigus.Nature reviews. Disease primers · 2017Review
- Setting the target for pemphigus vulgaris therapy.JCI insight · 2017Review
- Mechanisms of Autoantibody-Induced Pathology.Frontiers in immunology · 2017Review
- Crosstalk between Signaling Pathways in Pemphigus: A Role for Endoplasmic Reticulum Stress in p38 Mitogen-Activated Protein Kinase Activation?Frontiers in immunology · 2017Article
- Mechanisms of Disease: Pemphigus and Bullous Pemphigoid.Annual review of pathology · 2016Review
- Article
- Super-Resolution Microscopy Reveals Altered Desmosomal Protein Organization in Tissue from Patients with Pemphigus Vulgaris.The Journal of investigative dermatology · 2016Article
- Immune response in pemphigus and beyond: progresses and emerging concepts.Seminars in immunopathology · 2016Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by autoantibodies to the keratinocyte adhesion protein desmoglein 3 (Dsg3). Previous studies suggest that PV pathogenesis involves p38 mitogen-activated protein kinase-dependent and -independent pathways. However, p38 is a difficult protein to study and therapeutically target because it has four isoforms and multiple downstream effectors. In this study, we identify MAPKAP (mitogen-activated protein kinase-activated protein) kinase 2 (MK2) as a downstream effector of p38 signaling in PV and describe MK2-dependent and -independent mechanisms of blister formation using passive transfer of human anti-Dsg IgG4 mAbs to neonatal mice. In human keratinocytes, PV mAbs activate MK2 in a dose-dependent manner. MK2 is also activated in human pemphigus skin blisters, causing translocation of MK2 from the nucleus to the cytosol. Small-molecule inhibition of MK2 and silencing of MK2 expression block PV mAb-induced Dsg3 endocytosis in human keratinocytes. In addition, small-molecule inhibition and genetic deletion of p38α and MK2 inhibit spontaneous but not induced suprabasal blisters by PV mAbs in mouse passive transfer models. Collectively, these data suggest that MK2 is a key downstream effector of p38 that can modulate PV autoantibody pathogenicity. MK2 inhibition may be a valuable adjunctive therapy for control of pemphigus blistering.
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Registered trials
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.