Functional analyses of roles of tyrosine kinases/phosphatases in lymhpcyte signaling

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In this study, we have found that the proto-oncogene products, H-Ras and c-Myc, act co-operatively to induce homophilic cell adhesion of lymphocytes through the induction of VLA-4 activation and of VCAM-1 expression (Minami, Tanaka). It was also shown that Syk tyrosine kinase and SHP-2 tyrosine phosphatase play important roles in IL-2-induced signal transduction (O'Shea). It was found that an adaptor molecule, LAT is palmitoylated and sequestered at GEM, and is required for the development and activation of T lymphocytes (Samelson). An importance of GEM in T cell engagement was also elucidated (Kosugi). In this study, we have established an experimental system using exo utero method, aiming to examine the effects of tyrosine kinase/phosphatase inhibitors on lymphocyte development in vivo (Otani). We have also shown that a lymphocyte-specific tyrosine phosphatase, LC-PTP, inhibits ERK that is activated during T cell activation (Ogata). It was reported that topoisomerase II inhibitors induce apoptosis of lymphocytes. In this study, it was found that Lyn tyrosine kinase regulates positively the topoisomerase II inhibitor-induced apoptosis of lymphocytes (Yamamura). We have also examined a possible role of tyrosine phosphatases in the process of lymphocyte-macrophage interaction (Moriyama). It was shown that engagement of LFA-1 and of TCR results in a synergistic tyrosine phosphorylation of Fak tyrosine kinase (Umehara). In this collaborative study, we have exchanged results mutually, and have discussed about the respective results extensively. We have also discussed to plan our future collaborative experiments.