Studies on regulation of actin cytoskeleton by phosphatidylinositol-3 kinase and its application.

磷脂酰肌醇3激酶调控肌动蛋白细胞骨架的研究及其应用。

• 批准号: 14206009
• 负责人: FUKUI Yasuhisa
• 金额: $ 32.95万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14206009/
• 关键词: PI3 kinase; phosphatidylinositol; PIP_3; plextrin; cell polarity; G protein; cell adhesion; cell motility; PI3キナーゼ

Cell motility is often caused by cytoskeletal rearrangement. We found SWAP-70 as a protein which regulates actin rearrangement depending on phosphatidylinositol-3 kinase to be involved in membrane ruffling. SWAP-70 binds to activated Rac and F-actin. Kidney cells cultured from SWAP-70 deficient mice exhibits impaired membrane ruffling after EGF treatment. Def-6, a protein homologous to SWAP-70 lacks the F-actin binding site found in SWAP-70. This year, we explored the difference of these two proteins.The two proteins enhanced membrane ruffling when overexpressed in Cos7 cells, suggesting that these proteins are both involved in membrane ruffling. They both co-localized with activated Rac, however, the phenotypes were quite different. SWAP-70 induced membrane ruffling but Def-6 induced marked misshaping of the cells. The time lapse experiment revealed that this morphological change was reversible, suggesting that cells are quickly changing their shapes. These results suggest that the two proteins are highly homologous but they contributes to membrane ruffling in completely different ways. It is interesting to argue how the binding activity correlates with their functions.

细胞运动通常是由细胞骨架重排引起的。我们发现SWAP-70是一种依赖于磷脂酰肌醇-3激酶调节肌动蛋白重排的蛋白质，参与膜皱褶。SWAP-70与活化的Rac和F-肌动蛋白结合。从SWAP-70缺陷小鼠培养的肾细胞在EGF处理后表现出受损的膜皱褶。Def-6是一种与SWAP-70同源的蛋白质，缺乏在SWAP-70中发现的F-肌动蛋白结合位点。今年，我们探索了这两种蛋白质的差异，这两种蛋白质在Cos 7细胞中过表达时增强了膜褶皱，表明这些蛋白质都参与了膜褶皱。它们都与活化的Rac共定位，然而，表型是相当不同的。SWAP-70诱导细胞膜皱褶，而Def-6诱导细胞明显变形。延时实验表明，这种形态变化是可逆的，这表明细胞正在迅速改变它们的形状。这些结果表明，这两种蛋白质是高度同源的，但它们以完全不同的方式促进膜皱褶。有趣的是争论结合活性如何与它们的功能相关。

项目成果

Sorting nexin homologues are targets of phosphatidylinositol 3-phosphate in sporulation of Schizosaccharomyces pombe.

分选连接蛋白同源物是粟酒裂殖酵母孢子形成中磷脂酰肌醇 3-磷酸的靶标。

• 发表时间: 2004
• 期刊: Genes to Cells 9(6)
• 作者: Koga;T.;Onishi;M.;Nakamura;Y.;Nakamura;T.;Shimoda;C.et al.
• 通讯作者: C.et al.

Patterson, R.L., et al.: "Phospholipase C-γ is required for agonist-induced Ca^<2+> entry"Cell. 111. 529-541 (2002)

Patterson，R.L.等人：“激动剂诱导的Ca 2+ 进入需要磷脂酶C-γ”细胞。111. 529-541 (2002)

Onishi, M., et al.: "Importance of phosphatidylinositol 3-phosphate in sporulation of Schizosaccharomyces pombe"Biosci.Biotechnol.Biochem.. (in press).

Onishi, M., 等人：“磷脂酰肌醇 3-磷酸在粟酒裂殖酵母孢子形成中的重要性”Biosci.Biotechnol.Biochem..（出版中）。

Proteomic identification of Bcl2-associated athanogene 2 as a novel MAPK-activated protein kinase 2 substrate.

Bcl2 相关的 athanogene 2 作为一种新型 MAPK 激活蛋白激酶 2 底物的蛋白质组学鉴定。

• 发表时间: 2004
• 期刊: J Biol Chem. Oct 1;279(40)
• 作者: Ueda K;Kosako H;Fukui Y;Hattori S.
• 通讯作者: Hattori S.

Onishi, M., et al.: "Role of phosphatidylinositol 3-phosphate in formation of forespore membrane in Schizosaccharomyces pombe"Yeast. (in press).

Onishi, M., 等人：“磷脂酰肌醇 3-磷酸在粟酒裂殖酵母前孢子膜形成中的作用”酵母。