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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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Published in: | Immunity (Cambridge, Mass.) Mass.), 2010-08, Vol.33 (2), p.167-180 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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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.
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► 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 |
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ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/j.immuni.2010.08.001 |