| First Author | Hoff H | Year | 2007 |
| Journal | Eur J Immunol | Volume | 37 |
| Issue | 4 | Pages | 1072-86 |
| PubMed ID | 17330819 | Mgi Jnum | J:120716 |
| Mgi Id | MGI:3707891 | Doi | 10.1002/eji.200636240 |
| Citation | Hoff H, et al. (2007) The tyrosine phosphatase SHP-2 regulates differentiation and apoptosis of individual primary T lymphocytes. Eur J Immunol 37(4):1072-86 |
| abstractText | 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. |
