We previously demonstrated that the Fc receptor γ-chain Y
58(C-terminal tyrosine) is highly susceptible to dephosphorylation; a mechanism that controls the extent of Syk activation and the downstream signaling in mast cells. Here, we explored the importance of the γ-chain Y
47
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We previously demonstrated that the Fc receptor γ-chain Y
58(C-terminal tyrosine) is highly susceptible to dephosphorylation; a mechanism that controls the extent of Syk activation and the downstream signaling in mast cells. Here, we explored the importance of the γ-chain Y
47 (N-terminal tyrosine) in mast cell signaling. We generated a highly sensitive and versatile phospho-specific antibody that recognized the phosphorylated Y
47 in various species. Using this antibody, we found that mutation of the FcεRIβ Y
219 to phenylalanine caused a loss in the phosphorylation of the γ-chain Y
47, consistent with the previously described role of Y
219 in Lyn association with FcεRIβ and subsequent FcεRIγ phosphorylation. These conditions also diminished the tyrosine phosphorylation of Syk and LAT1 but, surprisingly, not the phosphorylation of Akt at T
308. Mutation of Y
47 or Y
58 of the γ-chain also caused a marked inhibition of Syk and LAT1 phosphorylation, but only the latter mutant showed a reduction in Akt phosphorylation. These findings show that the full phosphorylation of Syk and LAT1 requires the FcεRIβ Y
219 and both Y
47 and Y
58 of the γ-chain. However, T
308 phosphorylation of Akt is largely independent of FcεRIγ Y
47 phosphorylation and of the Lyn-binding site (Y
219) on the FcεRIβ.
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