2016 Fiscal Year Final Research Report
Comprehensive understanding of intracellular signaling pathways deregulated by CagA, the oncogenic scaffold protein from H. pylori
| Project/Area Number |
25250016
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | ヘリコバクター・ピロリ / 胃がん / CagA / SHP2 / チロシンリン酸化 / 感染発がん |
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| 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.
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| Free Research Field |
感染腫瘍学
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