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• W4242455889 endingPage "2205" @default.
• W4242455889 startingPage "2199" @default.
• W4242455889 abstract "Cross-linking of IgE or a bacterial product (f-Met-Leu-Phe; FMLP) induces the release of leukotriene C4 (LTC4) and histamine in human basophils. However, the signaling mechanisms in human basophils are only partially understood. It has been demonstrated that extracellular signal-regulated kinases (ERK1/2) specifically regulate the pathway for LTC4 generation, but not for histamine release and interleukin-4 production. More recent studies have suggested that tyrosine kinase (syk)-mediated phosphorylation of shc is responsible for the ras-ERK cascade via the formation of shc-Grb2-Sos2 following stimulation with anti-IgE antibody, but not FMLP, in human basophils. However, while characterizing the role of phosphatidylinositol (PI)-3 kinase in signaling pathways leading to basophil mediator release, it was noted that this pathway might also regulate p21ras activation. Anti-IgE antibody, but not FMLP, resulted in phosphorylation of p85 (regulatory subunit of PI3 kinase), suggesting activation of PI3 kinase. Inhibition of PI3 kinase by selective inhibitor (LY294002) abolished anti-IgE antibody- but not FMLP-induced phosphorylation of MEK1 (MAPK kinase/ERK kinase) and ERKs while inhibiting LTC4 generation as well as histamine release. IgE-mediated activation of ras (upstream of MEK-ERK) was also inhibited. But, further upstream, phosphorylation of syk and of shc and inducible association between shc and Grb2 were not affected. Furthermore, the IgE-mediated cytosolic calcium response ([Ca++]i) was also diminished. These results suggest that functional responses may be dependent on the activity of PI3 kinase, which regulates at least 2 important signaling pathways: by regulating activation of ras for the MEK-ERK pathway and the increase in [Ca++]i." @default.
• W4242455889 created "2022-05-12" @default.
• W4242455889 creator A5023714019 @default.
• W4242455889 creator A5081046119 @default.
• W4242455889 date "2000-09-15" @default.
• W4242455889 modified "2023-09-28" @default.
• W4242455889 title "Phosphatidylinositol-3 kinase regulates p21ras activation during IgE-mediated stimulation of human basophils" @default.
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• W4242455889 doi "https://doi.org/10.1182/blood.v96.6.2199.h8002199_2199_2205" @default.
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