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- W4313344833 abstract "Abstract Although SHP-1, a cytoplasmic protein tyrosine phosphatase (PTP), is shown to be a negative modulator in hematopoietic cells, its precise molecular mechanisms are not well defined. To clarify how SHP-1 regulates FcεRI-mediated signaling in mast cells, we generated bone marrow-derived mast cells (BMMC) from motheaten (me) that lack SHP-1 expression, viable motheaten (mev) that express phosphatase-deficient form of SHP-1, and control (WT) mice and examined downstream signaling events and final outputs following FcεRI crosslinking. FcεRI-induced tyrosine phosphorylation of SLP-76 and LAT, activation of MAPKs, and cytokine production were increased in me- and mev-derived BMMC, in good accordance with the previous implication of SHP-1 as a negative regulator. Since the activity of Syk that is responsible for the phosphorylation of SLP-76 and LAT was comparable in all BMMCs, both molecules might be substrates of SHP-1 in mast cells. In contrast, me-BMMC showed severely impaired PLCγ phosphorylation, FcεRI-induced calcium mobilization, especially extracellular calcium entry, and degranulation. We could not observe these phenotypes in mev-BMMC, thus suggesting that the expression of SHP-1, irrespective PTP activity, is sufficient for the positive regulation of these pathways. The absence of SHP-1 expression disrupted the association between SLP-76 and PLCγ, which might explain, at least in part, the decrease of calcium response in me-BMMC. Collectively, all these results suggest that SHP-1 regulates FcεRI-induced downstream signaling events both negatively and positively by functioning as a PTP and an adaptor protein contributing to the formation of signaling complex, respectively." @default.
- W4313344833 created "2023-01-06" @default.
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- W4313344833 date "2009-04-01" @default.
- W4313344833 modified "2023-09-23" @default.
- W4313344833 title "Dissection of the SHP-1 functions in FcεRI signaling (139.8)" @default.
- W4313344833 doi "https://doi.org/10.4049/jimmunol.182.supp.139.8" @default.
- W4313344833 hasPublicationYear "2009" @default.
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