| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
ITD-Flt3 enhance cell migration toward the chemokine CXCL12/SDF1. A comparison of the CXCL12-induced gene expression between ITD-Flt3+ and ITD-Flt3- Ba/F3 cells revealed that one of the genes that was differentially regulated by CXCL12 depending on the Flt3 status was Rock1. The expression of Rock1 in the ITD-Flt3+ cells that migrated toward CXCL12 was significantly higher than in ITD-Flt3- cells that migrated toward CXCL12. In ITD-Flt3- cells, Rock1 expression and MYPT1 phosphorylation were transiently up-regulated but were subsequently down-regulated by CXCL12. In contrast, the presence of ITD-Flt3 blocked the CXCL12-induced down-regulation of Rock1 and early MYPT1 dephosphorylation. Rock1 antagonists or Rock1 shRNA abolished the enhanced migration of ITD-Flt3+ cells toward CXCL12. Our findings demonstrate that ITD-Flt3 increases cell migration toward CXCL12 by antagonizing the down-regulation of Rock1 expression.
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