|Budget Amount *help
¥46,280,000 (Direct Cost: ¥35,600,000、Indirect Cost: ¥10,680,000)
Fiscal Year 2016: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2015: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2014: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2013: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
|Outline of Final Research Achievements
We found that the intracellular localization of SHP2, a key cellular target of the Helicobacter pylori CagA oncoprotein, is regulated by binding with the Hippo signal effectors, TAZ and YAP. We also found that parafibromin, a newly identified SHP2 substrate, acts as a transcriptional scaffold that integrates multiple distinct morphogen signals and converts them into adequate transcriptional outputs.
We identified SHP1 as a phosphatase that dephosphorylates CagA on the EPIYA motifs and thereby neutralizes the oncogenic potential of CagA. Meanwhile Pragmin, a human EPIYA-containing protein, was found to interact with and thereby catalytically activate Csk. H. pylori CagA may additionally promote neoplastic transformation of cells by perturbing the Pragmin-Csk signaling axis.