XXXX is a phosphatase that negatively regulates @entity6755 and T cell receptor signaling pathways.

@entity1522 @entity19176 @entity16055 @entity72769 @entity367 @entity669 @entity6755
T cell activity is controlled in large part by the T cell receptor (TCR). The TCR detects the presence of foreign pathogens and activates the T cell-mediated immune reaction. Numerous intracellular signaling pathways downstream of the TCR are involved in the process of T cell activation. Negative regulation of these pathways helps prevent excessive and deleterious T cell responses. Two homologous proteins, @entity19176 and @entity72769 , have been shown to function as critical negative regulators of TCR signaling. The @entity16055 mutase-like domain of @entity19176 ( @entity19176 ) has a potent phosphatase activity that contributes to the suppression of TCR signaling. The function of @entity72769 ( @entity19176 ) as a phosphatase has been less clear, principally because its intrinsic enzyme activity has been difficult to detect. Here, we demonstrate that @entity72769 regulates the level of @entity669 phosphorylation on targets within T cells, among them the critical T cell @entity669 kinase @entity6755 . Utilizing new phosphorylated substrates, we demonstrate that @entity72769 ( @entity19176 ) has clear, albeit weak, phosphatase activity. We further pinpoint @entity72769 residues @entity367 -481, Ser-552, and Ser-582 as specificity determinants, in that an @entity72769 ( @entity19176 ) triple mutant in which these three @entity1522 are altered to their counterparts in @entity19176 has substantially increased activity. Our results suggest that the phosphatase activities of both suppressor of TCR signaling homologues cooperate in a similar but independent fashion to help set the threshold for TCR-induced T cell activation.
