Cell Signaling Technology

Product Pathways - Lymphocyte Signaling

PTPN22 Antibody #12447

Applications Reactivity Sensitivity MW (kDa) Source
W IP H Endogenous 98 Rabbit

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

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.

Western Blotting

Western Blotting

Western blot analysis of extracts from Daudi and NK-92 cells using PTPN22 Antibody.

Western Blotting

Western Blotting

Western blot analysis of extracts from 293T cells, mock transfected (-) or transfected with a construct expressing Myc/DDK-tagged full-length human PTPN22 (hPTPN22-Myc/DDK; +), using PTPN22 Antibody.

IP

IP

Immunoprecipitation of PTPN22 from Daudi cell extracts, using Normal Rabbit IgG #2729 (lane 2) or PTPN22 Antibody (lane 3). Lane 1 is 10% input. Western blot analysis was performed using PTPN22 Antibody.


Background

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.

Application References

Have you published research involving the use of our products? If so we'd love to hear about it. Please let us know!

Companion Products

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

Products