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98 Rabbit

Product Usage Information

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody.

Specificity / Sensitivity

PTPN22 Antibody recognizes endogenous levels of total PTPN22 protein.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding His301 of human PTPN22 protein. Antibodies are purified by protein A and peptide affinity chromatography.

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).

1.  Cohen, S. et al. (1999) Blood 93, 2013-24.

2.  Matthews, R.J. et al. (1992) Mol Cell Biol 12, 2396-405.

3.  Cloutier, J.F. and Veillette, A. (1996) EMBO J 15, 4909-18.

4.  Cloutier, J.F. and Veillette, A. (1999) J Exp Med 189, 111-21.

5.  Hasegawa, K. et al. (2004) Science 303, 685-9.

6.  Bottini, N. et al. (2004) Nat Genet 36, 337-8.

7.  Begovich, A.B. et al. (2004) Am J Hum Genet 75, 330-7.

8.  Kyogoku, C. et al. (2004) Am J Hum Genet 75, 504-7.

9.  Velaga, M.R. et al. (2004) J Clin Endocrinol Metab 89, 5862-5.

10.  Vang, T. et al. (2005) Nat Genet 37, 1317-9.

11.  Rieck, M. et al. (2007) J Immunol 179, 4704-10.

12.  Zhang, J. et al. (2011) Nat Genet 43, 902-7.

Entrez-Gene Id 26191
Swiss-Prot Acc. Q9Y2R2

For Research Use Only. Not For Use In Diagnostic Procedures.
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