Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases
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- Stanford, S.M., Mustelin, T.M. & Bottini, N. Semin Immunopathol (2010) 32: 127. doi:10.1007/s00281-010-0201-4
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A relatively large number of protein tyrosine phosphatases (PTPs) are known to regulate signaling through the T cell receptor (TCR). Recent human genetics studies have shown that several of these PTPs are encoded by major autoimmunity genes. Here, we will focus on the lymphoid tyrosine phosphatase (LYP), a critical negative modulator of TCR signaling encoded by the PTPN22 gene. The functional analysis of autoimmune-associated PTPN22 genetic variants suggests that genetic variability of TCR signal transduction contributes to the pathogenesis of autoimmunity in humans.