ArticleThe Journal of biological chemistry2008
Differential dephosphorylation of the FcRgamma immunoreceptor tyrosine-based activation motif tyrosines with dissimilar potential for activating Syk.
Article in The Journal of biological chemistry, 2008. 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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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.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Reduced late endosome/lysosome function promotes SLE through chronic PI3K activity and SHP-1/SHIP-1 defects.JCI insight · 2026Article
- Docking of Syk to FcεRI is enhanced by Lyn but limited in duration by SHIP1.Molecular biology of the cell · 2022Article
- Combinatorial diversity of Syk recruitment driven by its multivalent engagement with FcεRIγ.Molecular biology of the cell · 2019Article
- A Precision B Cell-Targeted Therapeutic Approach to Autoimmunity Caused by Phosphatidylinositol 3-Kinase Pathway Dysregulation.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Importance of Fc Receptor γ-Chain ITAM Tyrosines in Neutrophil Activation andFrontiers in immunology · 2019Article
- CD45 exclusion- and cross-linking-based receptor signaling together broaden FcεRI reactivity.Science signaling · 2018Article
- Differential mast cell outcomes are sensitive to FcεRI-Syk binding kinetics.Molecular biology of the cell · 2017Article
- Regulation of FcRγ function by site-specific serine phosphorylation.Journal of leukocyte biology · 2017Article
- The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation.Nature communications · 2016Article
- Continuous inhibitory signaling by both SHP-1 and SHIP-1 pathways is required to maintain unresponsiveness of anergic B cells.The Journal of experimental medicine · 2016Article
- Of ITIMs, ITAMs, and ITAMis: revisiting immunoglobulin Fc receptor signaling.Immunological reviews · 2015Review
- Type II phosphatidylinositol 4-kinases interact with FcεRIγ subunit in RBL-2H3 cells.Molecular and cellular biochemistry · 2014Article
- Article
- Rethinking the role of immunoglobulin E and its high-affinity receptor: new insights into allergy and beyond.International archives of allergy and immunology · 2014Review
- Phosphatase regulation of immunoreceptor signaling in T cells, B cells and mast cells.Current opinion in immunology · 2013Review
- Article
- Functional analysis of Lyn kinase A and B isoforms reveals redundant and distinct roles in Fc epsilon RI-dependent mast cell activation.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- The tyrosine kinase network regulating mast cell activation.Immunological reviews · 2009Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The cell surface-expressed gamma chain of the high affinity receptor for IgE (FcepsilonRI) can be phosphorylated on two tyrosine residues of the immunoreceptor tyrosine-based activation motif (ITAM), leading to recruitment and activation of spleen tyrosine kinase (Syk), a kinase that is essential for mast cell signaling and allergic responses. However, it is not known whether preferential phosphorylation or dephosphorylation of the two individual FcRgamma tyrosines (the N-terminal Tyr47 and C-terminal Tyr58) could regulate Syk activation. Herein we report that phosphorylation of only Tyr58 was able to elicit Syk phosphorylation and a weak rise in intracellular calcium, suggesting that Tyr58 phosphorylation may be distinctively important for Syk activation. In vitro and in vivo studies revealed that both Tyr47 and Tyr58 could be similarly phosphorylated. However, mass spectrometric analysis of the phosphorylated FcepsilonRgamma from bone marrow-derived mast cells showed that phosphorylation at Tyr47 was at least 2-fold greater than at Tyr58. This suggested that, once phosphorylated, Tyr58 is preferentially dephosphorylated. In vitro studies demonstrated more efficient dephosphorylation of Tyr58 (by the receptor-associated phosphatases SHP-1 and SHP-2) than of Tyr47. Analysis of Syk binding to wild type and mutant phosphorylated FcepsilonRI revealed that mutation at Tyr58 almost completely ablated Syk binding, whereas mutation at Tyr47 moderately reduced Syk binding. The findings argue for a novel regulatory mechanism, where dephosphorylation of phospho-Tyr58 is likely to promote the down-regulation of Syk activation and suppression of mast cell responses.
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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.