The tyrosine phosphatase SHP-2 regulates differentiation and apoptosis of individual primary T lymphocytes.
Although phosphatases are key players of intracellular processes, not much is known about the phosphatase SHP-2 during T cell differentiation. Here we show that ectopic over-expression of SHP-2 in primary T helper cells directly reduced the frequency of individual lymphocytes expressing pro-inflammatory cytokines after antigen-specific stimulation by a mechanism impairing ... activation of protein kinase C. In addition we demonstrate that SHP-2 mediates enhanced migration upon CXCR4 signaling in a G-protein-dependent manner. Most strikingly, SHP-2 mediated a dramatic increase in apoptosis by highly enhanced activation of caspases. Co-immunoprecipitations of SHP-2 and c-Cbl from primary T helper cells demonstrated that SHP-2 strongly interacts with the ubiquitin ligase c-Cbl, indicating that c-Cbl could mediate the negative signals of SHP-2. Our results show that SHP-2 signal transduction regulates central checkpoints of T cell differentiation by the activation of distinct signaling cascades.
Mesh Terms:
Animals, Apoptosis, Cell Differentiation, Cell Line, Cells, Cultured, Intracellular Signaling Peptides and Proteins, Isoenzymes, Mice, Mice, Inbred BALB C, Mice, Transgenic, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatases, Signal Transduction, T-Lymphocytes, Helper-Inducer
Animals, Apoptosis, Cell Differentiation, Cell Line, Cells, Cultured, Intracellular Signaling Peptides and Proteins, Isoenzymes, Mice, Mice, Inbred BALB C, Mice, Transgenic, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatases, Signal Transduction, T-Lymphocytes, Helper-Inducer
Eur. J. Immunol.
Date: Apr. 01, 2007
PubMed ID: 17330819
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