| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
We previously demonstrated that serine/threonine kinase, protein kinase D (PKD) plays a crucial role in CD4+ T cell development by generating T cell-specific PKD deficient mice and found tyrosine phosphatase SHP-1 as a substrate of PKD in thymocytes. We generated phosphorylation-defective mutant SHP-1 knock-in mice (KI) to reveal the contribution of TCR-PKD-SHP-1 axis in CD4+ T cell development. Indeed, phosphorylation of SHP-1 was not observed in thymocytes from KI mice. In competitive bone marrow (BM) chimera mice of WT and KI BM, generation of CD4+ T cells from KI cells was impaired, indicating that phosphorylation of SHP-1 by PKD is critical for CD4+ T cell development. Phosphatase activity and localization of SHP-1 was not affected by the mutation. We also analyzed PKD and SHP-1 multiple knockout mice and revealed that impaired TCR signaling by PKD deficiency was slightly restored in these mice, suggesting that PKD regulates the function of SHP-1 through unknown mechanisms.
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