Research Abstract |
Our results are summarized as follows: 1. Regulation of cytokine signaling by PTPεC (1) PTPεC strongly suppressed IL-6-induced M1 differentiation in PTPεC activity-dependent manner. This suppression is due to suppression of JAK-activation. (2) This suppression by PTPεC was observed in STAT-activation through IL6R and IL10R, but not in those via IFNα/βR and IFNγR. 2. Structure and function of a novel dual specificity phosphatase, MKP-7 (1) MKP-7 has Rhodariese domain, catalytic domain, NLS, and NES. (2) Substrate specificity is in the order ot JNK>p38>>ERK. (3) MKP-7 is a shuttle protein between cytosol and nucleus. 3. Structure and function of a novel PP1-inhibitor, 1-4 (1) 1-4 strongly inhibits PP1, IC_<50> being 0.2 nM. (2) 1-4interacts with PP1C on at least three sites. 4. Structure-function relationship of tautomycin and its related compounds (1) Different moieties of tautomycin are involved in protein phosphatase inhibition and induction of apoptosis. (2) Tautomycetin is found to be a strong and specific inhibitor for PP1.
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