PTPN22 Antibody #12447

PTPN22 (Lyp/PEP) is a cytoplasmic phosphatase expressed by hematopoietic cells (1,2). PTPN22 associates with the tyrosine kinase Csk to inhibit T cell receptor signaling through inactivation of Src kinases (3,4). Csk phosphorylates Src kinases on an inhibitory tyrosine, while PTPN22 dephosphorylates an activating site (4). PTPN22^(-/-) mice have higher levels of activated Lck than wild-type, resulting in greater T cell expansion and increased serum antibody levels (5). Research studies have shown that a single-nucleotide polymorphism, 1858T of the PTPN22 gene which encodes the amino acid substitution R620W, confers increased risk for multiple autoimmune diseases including type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, and Graves disease (6-9). Interestingly, although the R620W substitution disrupts the interaction between Csk and PTPN22, it is actually a gain-of-function mutation resulting in increased phosphatase activity (6,10,11). Recent evidence suggests that the autoimmune phenotype associated with the R620W variant is the result of increased calpain-mediated degradation and decreased protein levels of PTPN22 (12).