  Lipid raft targeting of hematopoietic protein tyrosine phosphatase by protein kinase C theta-mediated phosphorylation.; ; et al in Molecular & Cellular Biology (2006), 26(5), 1806-16 Protein kinase C theta (PKC theta) is unique among PKC isozymes in its translocation to the center of the immune synapse in T cells and its unique downstream signaling. Here we show that the hematopoietic ... [more ▼] Protein kinase C theta (PKC theta) is unique among PKC isozymes in its translocation to the center of the immune synapse in T cells and its unique downstream signaling. Here we show that the hematopoietic protein tyrosine phosphatase (HePTP) also accumulates in the immune synapse in a PKC theta-dependent manner upon antigen recognition by T cells and is phosphorylated by PKC theta at Ser-225, which is required for lipid raft translocation. Immune synapse translocation was completely absent in antigen-specific T cells from PKC theta-/- mice. In intact T cells, HePTP-S225A enhanced T-cell receptor (TCR)-induced NFAT/AP-1 transactivation, while the acidic substitution mutant was as efficient as wild-type HePTP. We conclude that HePTP is phosphorylated in the immune synapse by PKC theta and thereby targeted to lipid rafts to temper TCR signaling. This represents a novel mechanism for the active immune synapse recruitment and activation of a phosphatase in TCR signaling. [less ▲] Detailed reference viewed: 32 (5 ULg)Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH.; ; et al in Journal of Biological Chemistry (2004), 279(6), 4922-8 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 ... [more ▼] 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. [less ▲] Detailed reference viewed: 10 (2 ULg)A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes.; ; et al in Nature Genetics (2004), 36(4), 337-8 We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes ... [more ▼] We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes mellitus (T1D). The variants encoded by the two alleles, 1858C and 1858T, differ in a crucial amino acid residue involved in association of LYP with the negative regulatory kinase Csk. Unlike the variant encoded by the more common allele 1858C, the variant associated with T1D does not bind Csk. [less ▲] Detailed reference viewed: 19 (8 ULg)Protein tyrosine phosphatases in T cell physiology.; ; et al in Molecular Immunology (2004), 41(6-7), 687-700 The molecular mechanisms of signal transduction have been the focus of intense research during the last decade. In T cells, much of the work has centered on protein tyrosine kinase-mediated signaling from ... [more ▼] The molecular mechanisms of signal transduction have been the focus of intense research during the last decade. In T cells, much of the work has centered on protein tyrosine kinase-mediated signaling from the TCR and cytokine receptors, while the study of protein tyrosine phosphatases has lagged behind. Nevertheless, it has now become clear that many protein tyrosine phosphatases play equally important roles in T cell physiology and that no kinase-regulated system would work without the counterbalancing participation of phosphatases. In fact, we have learned that many processes are regulated primarily on the phosphatase side. This minireview summarizes the current state-of-the art in our understanding of the regulation and biology of protein tyrosine phosphatases in T lymphocyte physiology. [less ▲] Detailed reference viewed: 22 (3 ULg)Role of protein tyrosine phosphatases in T cell activation.; Rahmouni, Souad  ; et alin Immunological Reviews (2003), 191 The last decade has seen an exponentially increasing interest in the molecular mechanisms of signal transduction. In T cells, much of the focus has been on protein tyrosine kinase (PTK)-mediated signaling ... [more ▼] The last decade has seen an exponentially increasing interest in the molecular mechanisms of signal transduction. In T cells, much of the focus has been on protein tyrosine kinase (PTK)-mediated signaling from the T cell receptor (TCR) and cytokine receptors, while the study of protein tyrosine phosphatases (PTPases) has lagged behind. However, recent discoveries have revealed that several PTPases play important roles in many different aspects of T cell physiology. We predict that the phosphatases will become a 'hot topic' in the field within the next few years. This review summarizes the current understanding of the regulation and biology of PTPases in T lymphocyte activation. [less ▲] Detailed reference viewed: 16 (3 ULg) |
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