The phosphatase PTP-PEST promotes secondary T cell responses by dephosphorylating the protein tyrosine kinase Pyk2.
PTP-PEST (encoded by Ptpn12) is an intracellular protein tyrosine phosphatase belonging to the same family as LYP. LYP inhibits secondary T cell responses by suppressing Src family protein tyrosine kinases and is implicated in human autoimmunity. To determine the function of PTP-PEST in T cells, we generated mice with a conditionally deleted allele of Ptpn12. By removing PTP-PEST in T cells, we determined that PTP-PEST was not necessary for T cell development or primary responses. However, PTP-PEST was required for secondary T cell responses, anergy prevention, and autoimmunity induction. PTP-PEST specifically regulated the phosphorylation of Pyk2, a substrate of the Src family kinase Fyn. It also promoted the formation of T cell homoaggregates, which are known to enhance T cell activation. Thus, PTP-PEST controls Pyk2 activity and is a positive regulator of secondary T cell activation. These data illustrate the critical role of protein tyrosine phosphatases in T cell regulation.
Davidson
Dominique
D
Laboratory of Molecular Oncology, Clinical Research Institute of Montréal, Montréal, Québec H2W 1R7, Canada. dominique.davidson@ircm.qc.ca
Shi
Xiaochu
X
Zhong
Ming-Chao
MC
Rhee
Inmoo
I
Veillette
André
A
D000818:Animals; D002449:Cell Aggregation; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051418:Focal Adhesion Kinase 2 / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
D009479:Neuropeptides; C484602:Rac1 protein, mouse; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein