Tyrosine phosphorylation of VHR phosphatase by ZAP-70.

DNA-Binding Proteins; Dual Specificity Phosphatase 3; Humans; JNK Mitogen-Activated Protein Kinases; Jurkat Cells; Lymphocyte Activation; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors; Mitogen-Activated Protein Kinases/antagonists & inhibitors; Mutagenesis, Site-Directed; Phosphorylation; Protein Tyrosine Phosphatases/chemistry/genetics/metabolism; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins/antagonists & inhibitors; Substrate Specificity; T-Lymphocytes/immunology/metabolism; Transcription Factors; Tyrosine/metabolism; ZAP-70 Protein-Tyrosine Kinase; ets-Domain Protein Elk-1

Abstract :

[en] The ZAP-70 tyrosine kinase is a key component of the signaling machinery for the T cell antigen receptor (TCR). Whereas recruitment and activation of ZAP-70 are relatively well understood, the proteins phosphorylated by ZAP-70 are incompletely known. We report here that VHR, a Vaccinia virus VH1-related dual-specific protein phosphatase that inactivates the mitogen-activated kinases Erk2 and Jnk, is phosphorylated at Y138 by ZAP-70. Tyr138 phosphorylation was required for VHR to inhibit the Erk2-Elk-1 pathway and, conversely, the VHR(Y138F) mutant augmented TCR-induced Erk2 kinase and activation of the gene encoding interleukin 2. These results suggest that VHR is a target for ZAP-70 and tempers activation of the Erk2 pathway in a ZAP-70-controlled manner.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Alonso, Andres

Rahmouni, Souad ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation

Williams, Scott

van Stipdonk, Marianne

Jaroszewski, Lukasz

Godzik, Adam

Abraham, Robert T

Schoenberger, Stephen P

Mustelin, Tomas

Language :

English

Title :

Tyrosine phosphorylation of VHR phosphatase by ZAP-70.

Publication date :

2003

Journal title :

Nature Immunology

ISSN :

1529-2908

eISSN :

1529-2916

Publisher :

Nature Publishing Group

Volume :

Issue :

Pages :

44-8

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 27 January 2009

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Bibliography

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