Article (Scientific journals)
Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH.
Alonso, Andres; Bottini, Nunzio; Bruckner, Shane et al.
2004In Journal of Biological Chemistry, 279 (6), p. 4922-8
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Keywords :
Amino Acid Sequence; Bacterial Outer Membrane Proteins/chemistry/genetics/metabolism; Humans; Jurkat Cells; Lymphocyte Activation; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/chemistry/metabolism; Molecular Sequence Data; Mutagenesis, Site-Directed; Phosphorylation; Protein Tyrosine Phosphatases/chemistry/genetics/metabolism; Receptors, Antigen, T-Cell/antagonists & inhibitors/metabolism; Recombinant Proteins/chemistry/genetics/metabolism; Signal Transduction; T-Lymphocytes/immunology/metabolism/microbiology; Tyrosine/chemistry; Virulence; Yersinia pestis/enzymology/genetics/pathogenicity
Abstract :
[en] A key virulence factor for Yersinia pestis, the etiologic agent of plague, is the tyrosine phosphatase YopH, which the bacterium injects into host cells. We report that treatment of human T lymphocytes with a recombinant membrane-permeable YopH resulted in severe reduction in intracellular tyrosine phosphorylation and inhibition of T cell activation. The primary signal transducer for the T cell antigen receptor, the Lck tyrosine kinase, was specifically precipitated by a substrate-trapping YopH mutant, and Lck was dephosphorylated at its positive regulatory site, Tyr-394, in cells containing active YopH. By turning off Lck, YopH blocks T cell antigen receptor signaling at its very first step, effectively preventing the development of a protective immune response against this lethal bacterium.
Disciplines :
Immunology & infectious disease
Biochemistry, biophysics & molecular biology
Author, co-author :
Alonso, Andres
Bottini, Nunzio
Bruckner, Shane
Rahmouni, Souad  ;  Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Williams, Scott
Schoenberger, Stephen P
Mustelin, Tomas
Language :
English
Title :
Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH.
Publication date :
2004
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
279
Issue :
6
Pages :
4922-8
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 January 2009

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