2012 Fiscal Year Final Research Report
Regulation of early embryonic PI3K activity:Implication of non-canonical PI3K interacting molecules and their roles in embryonic cellular functions
| Project/Area Number |
23880008
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KAMEI Hiroyasu 東京大学, 大学院・農学生命科学研究科, 特任研究員 (00610362)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 発生 |
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| Research Abstract |
Embryonic development is orchestrated by numerous growth factors and cytokines, including insulin-like growth factors. Phosphatidylinositol 3-kinase (PI3K) operates as a pivotal node in their cellular signaling cascades. Albeit its physiological relevance and importance is well acknowledged, little is known about the regulatory mechanisms of PI3K in early stages of embryogenesis. Here we examine the regulation of early embryonic PI3K by utilizing zebrafish embryo and mouse embryonic stem cell (mESC) models. Pharmacological blockade of PI3K activity in zebrafish embryo showed that the early embryonic PI3K particularly in the developmental stage preceding zygotic gene expression was prerequisite for embryonic survival whereas the inhibition at subsequent organogenesis stages caused developmental delay without causing severe lethality. In addition, the p85-bound PI3K activities in early zebrafish embryos were not limited simply by the p85 protein level nor by its bound phospho-tyrosine level. These data imply a previously unknown PI3K regulatory mechanism(s) in early embryogenesis which is important for embryonic survival. Indeed, LC-MS/MS analysis of p110 PI3K catalytic subunit immunoprecipitated from mESC lysate revealed several novel p110β associating molecules. Based on these results, we proposed an “embryo specific”PI3K regulatory mechanism, which is regulated by previously unknown PI3K-associated proteins.
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