ArticleThe Journal of biological chemistry2012
Novel mechanism for Fc{epsilon}RI-mediated signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation and the selective influence of STAT5B over mast cell cytokine production.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- The decoy oligodeoxynucleotide against HIF-1α and STAT5 ameliorates atopic dermatitis-like mouse model.Molecular therapy. Nucleic acids · 2023Article
- IgG:FcγRIIb signals block effector programs of IgE:FcεRI-activated mast cells but spare survival pathways.The Journal of allergy and clinical immunology · 2023Article
- GRK2 differentially regulates FcεRI and MRGPRB2-mediated responses in mast cells.Frontiers in immunology · 2023Article
- Review
- Stat5B is required for IgE-Mediated mast cell function in vitro and in vivo.Cellular immunology · 2021Article
- Anaphylaxis: Focus on Transcription Factor Activity.International journal of molecular sciences · 2021Review
- Article
- Effect of Xingbi Gel Nasal Drops on Fyn-STAT5 Pathway in Nasal Mucosa Fibroblasts of Guinea Pigs with Allergic Rhinitis.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Transcription Factors in the Development and Pro-Allergic Function of Mast Cells.Frontiers in allergy · 2021Review
- Article
- Oxidation Impacts the Intracellular Signaling Machinery in Hematological Disorders.Antioxidants (Basel, Switzerland) · 2020Review
- Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich's visions to precision medicine concepts.Theranostics · 2020Review
- Article
- Fyn kinase is a novel modulator of erythropoietin signaling and stress erythropoiesis.American journal of hematology · 2019Article
- FYN promotes mesenchymal phenotypes of basal type breast cancer cells through STAT5/NOTCH2 signaling node.Oncogene · 2018Article
- Article
- 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
- Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today.Frontiers in immunology · 2018Review
- Selective induction of alternatively spliced FynT isoform by TNF facilitates persistent inflammatory responses in astrocytes.Scientific reports · 2017Article
- Orai and TRPC channel characterization in FcPhysiological reports · 2017Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
Previous studies indicate that STAT5 expression is required for mast cell development, survival, and IgE-mediated function. STAT5 tyrosine phosphorylation is swiftly and transiently induced by activation of the high affinity IgE receptor, FcεRI. However, the mechanism for this mode of activation remains unknown. In this study we observed that STAT5 co-localizes with FcεRI in antigen-stimulated mast cells. This localization was supported by cholesterol depletion of membranes, which ablated STAT5 tyrosine phosphorylation. Through the use of various pharmacological inhibitors and murine knock-out models, we found that IgE-mediated STAT5 activation is dependent upon Fyn kinase, independent of Syk, PI3K, Akt, Bruton's tyrosine kinase, and JAK2, and enhanced in the context of Lyn kinase deficiency. STAT5 immunoprecipitation revealed that unphosphorylated protein preassociates with Fyn and that this association diminishes significantly during mast cell activation. SHP-1 tyrosine phosphatase deficiency modestly enhanced STAT5 phosphorylation. This effect was more apparent in the absence of Gab2, a scaffolding protein that docks with multiple negative regulators, including SHP-1, SHP-2, and Lyn. Targeting of STAT5A or B with specific siRNA pools revealed that IgE-mediated mast cell cytokine production is selectively dependent upon the STAT5B isoform. Altogether, these data implicate Fyn as the major positive mediator of STAT5 after FcεRI engagement and demonstrate importantly distinct roles for STAT5A and STAT5B in mast cell function.
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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.