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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2010-08, Vol.33 (2), p.167-180
Main Authors: Davidson, Dominique, Shi, Xiaochu, Zhong, Ming-Chao, Rhee, Inmoo, Veillette, André
Format: Article
Language:English
Subjects:
Animals
Cell adhesion & migration
Cell Aggregation
Cell Proliferation
CELLIMMUNO
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
Immune system
Lymphocyte Activation
Medical research
Mice
Mice, Inbred C57BL
Mice, Knockout
MOLIMMUNO
Neuropeptides - metabolism
Peptides
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
Proteins
rac GTP-Binding Proteins - metabolism
rac1 GTP-Binding Protein
Rodents
T cell receptors
T-Lymphocytes - cytology
T-Lymphocytes - enzymology
T-Lymphocytes - immunology
Transgenic animals
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Summary: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. [Display omitted] ► PTP-PEST is not required for T cell development or primary T cell responses ► In T cells, PTP-PEST specifically dephosphorylates Pyk2, a Fyn substrate ► PTP-PEST promotes LFA-1 activation and the formation of T cell homoconjugates ► PTP-PEST is necessary for secondary T cell responses, anergy and autoimmunity
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2010.08.001