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• W2142454776 endingPage "7037" @default.
• W2142454776 startingPage "7027" @default.
• W2142454776 abstract "Abstract Mediator release from human basophils is a self-limited process, but down-regulation of the signaling cascades leading to secretion of leukotriene C4 (LTC4) is controlled independently of the pathway leading to IL-4 secretion. In the current studies, we have explored the regulation of upstream signaling events leading to activation of extracellular signal-related kinases (ERKs; previously shown to be required for LTC4 generation) in human basophils. IgE-, but not FMLP-mediated activation, induced sustained tyrosine phosphorylation of syk, of shc, and an association of shc to the Grb2/son of sevenless 2 complex. In contrast, IgE-mediated activation resulted in transient activation of p21ras and mitogen-activated protein/ERK kinase 1, which were kinetically associated with phosphorylation of ERKs. The canonical Shc/Grb2/son of sevenless pathway to activation of p21ras is therefore sustained, while p21ras activity is not. We have previously shown that phosphatidylinositol 3 kinase activity is required for p21ras activity and, in the current studies, we show that of the p85-sensitive forms of p110 possible, basophils express only p110 δ and that there are no changes in association between p21ras and p110 δ in stimulated basophils. We used the generation of phospho-Akt as a marker of the presence of phosphatidylinositol-3,4,5-trisphosphate and found that phospho-Akt is transient on a time scale consistent with p21ras activity. On the basis of information obtained in these and other studies, we localize down-regulation of IgE-mediated LTC4 secretion to a region of the signaling cascade antecedent to p21ras activation, downstream of phosphatidylinositol 3 kinase activity and probably involving regulation of phosphatidylinositol-3,4,5-trisphosphate levels." @default.
• W2142454776 created "2016-06-24" @default.
• W2142454776 creator A5023714019 @default.
• W2142454776 creator A5045845592 @default.
• W2142454776 creator A5081046119 @default.
• W2142454776 date "2001-12-15" @default.
• W2142454776 modified "2023-10-14" @default.
• W2142454776 title "Localizing a Control Region in the Pathway to Leukotriene C4 Secretion Following Stimulation of Human Basophils with Anti-IgE Antibody" @default.
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• W2142454776 doi "https://doi.org/10.4049/jimmunol.167.12.7027" @default.
• W2142454776 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11739523" @default.
• W2142454776 hasPublicationYear "2001" @default.
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