| Budget Amount *help |
¥153,010,000 (Direct Cost: ¥117,700,000、Indirect Cost: ¥35,310,000)
Fiscal Year 2013: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Fiscal Year 2012: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Fiscal Year 2011: ¥70,980,000 (Direct Cost: ¥54,600,000、Indirect Cost: ¥16,380,000)
Fiscal Year 2010: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2009: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
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| Research Abstract |
The thrombopoietin (TPO) receptor, Mpl, is a cytokine receptor regulating platelet production and early hematopoiesis. Although TPO signaling is initiated by phosphorylation of optimally oriented Mpl dimers, dimerization of Mpl is poorly understood. Here, we describe the regulatory mechanism of dimerization of Mpl by single-molecule fluorescence imaging in live cells. Mpl molecules were associated and dissociated repeatedly on the plasma membrane. As a result, Mpl existed as a mixture of monomers, dimers, and oligomers. TPO increased Mpl dimers or oligomers by stabilizing Mpl dimers. The stabilization of Mpl dimers was dependent on their phosphorylation and an adaptor protein, Shc, suggesting that phosphorylated Mpl dimers were crosslinked by Shc. In contrast, knockdown of Shc, an Mpl transmembrane mutant, influenced their phosphorylation. Thus, phosphorylation of Mpl was regulated by the stability of Mpl dimers in a positive feedback manner.
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