Abstract
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.
Copyright 2010 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Aggregation
-
Cell Proliferation
-
Encephalomyelitis, Autoimmune, Experimental / enzymology
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Encephalomyelitis, Autoimmune, Experimental / immunology
-
Encephalomyelitis, Autoimmune, Experimental / pathology
-
Focal Adhesion Kinase 2 / immunology*
-
Focal Adhesion Kinase 2 / metabolism*
-
Lymphocyte Activation*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Neuropeptides / metabolism
-
Phosphorylation
-
Protein Tyrosine Phosphatase, Non-Receptor Type 12 / deficiency
-
Protein Tyrosine Phosphatase, Non-Receptor Type 12 / immunology*
-
Protein Tyrosine Phosphatase, Non-Receptor Type 12 / metabolism*
-
T-Lymphocytes / cytology
-
T-Lymphocytes / enzymology
-
T-Lymphocytes / immunology*
-
rac GTP-Binding Proteins / metabolism
-
rac1 GTP-Binding Protein
Substances
-
Neuropeptides
-
Rac1 protein, mouse
-
Focal Adhesion Kinase 2
-
Ptk2b protein, mouse
-
Protein Tyrosine Phosphatase, Non-Receptor Type 12
-
rac GTP-Binding Proteins
-
rac1 GTP-Binding Protein