ArticleMolecular and cellular biology2014
Transmembrane adaptor protein PAG/CBP is involved in both positive and negative regulation of mast cell signaling.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- KIRA6 is an Effective and Versatile Mast Cell Inhibitor of IgE-mediated Activation.European journal of immunology · 2025Article
- Changing the location of proteins on the cell surface is a promising strategy for modulating T cell functions.Immunology · 2024Review
- Article
- Neutralization of the adaptor protein PAG by monoclonal antibody limits murine tumor growth.Molecular therapy. Methods & clinical development · 2022Article
- The role of nitric oxide in the dorsomedial periaqueductal gray (dmPAG) column in cardiovascular responses in urethane-anesthetized male rats.Animal models and experimental medicine · 2022Article
- Transmembrane adaptor protein PAG is a mediator of PD-1 inhibitory signaling in human T cells.Communications biology · 2021Article
- Mast Cell Migration and Chemotaxis Assayed by Microscopy.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Article
- Cytoskeletal Protein 4.1R Is a Positive Regulator of the FcεRI Signaling and Chemotaxis in Mast Cells.Frontiers in immunology · 2019Article
- Positive and Negative Regulatory Roles of C-Terminal Src Kinase (CSK) in FcεRI-Mediated Mast Cell Activation, Independent of the Transmembrane Adaptor PAG/CSK-Binding Protein.Frontiers in immunology · 2018Article
- Domain interactions of C-terminal Src Kinase determined through NMR spectroscopy with segmental isotope labeling.Protein & cell · 2017Article
- Signal transduction and chemotaxis in mast cells.European journal of pharmacology · 2016Review
- New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling.Molecular and cellular biology · 2016Article
- Negative regulatory roles of ORMDL3 in the FcεRI-triggered expression of proinflammatory mediators and chemotactic response in murine mast cells.Cellular and molecular life sciences : CMLS · 2016Article
- Tetraspanins and Transmembrane Adaptor Proteins As Plasma Membrane Organizers-Mast Cell Case.Frontiers in cell and developmental biology · 2016Review
- Long-Range Modulation of PAG1 Expression by 8q21 Allergy Risk Variants.American journal of human genetics · 2015Article
- Article
- The Fyn-ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells.Frontiers in immunology · 2015Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transmembrane adaptor protein PAG/CBP (here, PAG) is expressed in multiple cell types. Tyrosine-phosphorylated PAG serves as an anchor for C-terminal SRC kinase, an inhibitor of SRC-family kinases. The role of PAG as a negative regulator of immunoreceptor signaling has been examined in several model systems, but no functions in vivo have been determined. Here, we examined the activation of bone marrow-derived mast cells (BMMCs) with PAG knockout and PAG knockdown and the corresponding controls. Our data show that PAG-deficient BMMCs exhibit impaired antigen-induced degranulation, extracellular calcium uptake, tyrosine phosphorylation of several key signaling proteins (including the high-affinity IgE receptor subunits, spleen tyrosine kinase, and phospholipase C), production of several cytokines and chemokines, and chemotaxis. The enzymatic activities of the LYN and FYN kinases were increased in nonactivated cells, suggesting the involvement of a LYN- and/or a FYN-dependent negative regulatory loop. When BMMCs from PAG-knockout mice were activated via the KIT receptor, enhanced degranulation and tyrosine phosphorylation of the receptor were observed. In vivo experiments showed that PAG is a positive regulator of passive systemic anaphylaxis. The combined data indicate that PAG can function as both a positive and a negative regulator of mast cell signaling, depending upon the signaling pathway involved.
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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.