Dynamic reorganization of cytoskeletion by WASP family proteins
Dynamic reorganization of cytoskeletion by WASP family proteins
批准号:
12307003
负责人:
TAKENAWA Tadaomi
金额:
$26.0万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (A)
财政年份:
2000
资助国家:
日本
项目状态:
已结题
起止时间:
2000 至 2002
中文摘要
众所周知,各种细胞对各种刺激作出反应,重新排列细胞骨架,为细胞分裂做准备,并刺激运动和迁移。细胞的定向迁移是生命的基本现象之一,包括向炎症部位的迁移以及癌细胞的侵袭和转移,我们发现了与细胞骨架重组和细胞迁移相关的WASP和WAVE蛋白。所有这些蛋白在C末端都有VCA区,其中V区与肌动蛋白结合,CA区与Arp2/3复合体结合。因此,这些蛋白质使肌动蛋白细丝成核,并促进肌动蛋白聚合。另一方面,在N-末端区域,有调控分子结合的区域。N-WASP与WIP、WISH、CDC42和PIP2等分子结合,WAVE与IRSP53结合,随后暴露这些蛋白的VCA区。因此,这些蛋白质结合到Arp2/3复合体上,并聚合肌动蛋白细丝。最后,位于Cdc42下游的N-WASP诱导丝状足的形成。位于RAC下游的波会诱导片状脂膜的形成。这些蛋白质存在于移动细胞的前沿,并产生驱动力。
英文摘要
It is already well known that a variety of cells rearrange cytoskeleton, prepare for cell division, and stimulate motility and migration in response to various stimuli. The directed migration of cells is one of fundamental phenomena of life, including migration toward inflammatory sites, and invasion and metastasis of cancer cells.We found WASP and WAVE proteins which are related to cytoskeleton reorganization and cell migration. All these proteins have VCA regions at C-terminal area in which V region binds actin and CA region binds Arp2/3 complex. As a result, these proteins nucleate actin filaments and enhance actin polymerization. On the other hand, at N-terminal area, there are regions to which regulatory molecules bind. N-WASP binds several molecules such as WIP, WISH, Cdc42 and PIP2, and WAVE binds IRSp53, followed by the exposure of VCA region of these proteins. Consequently, these proteins bind to Arp2/3 complex and polymerize actin filaments. Finally, N-WASP which is located downstream of Cdc42 induces filopodia formation. WAVE which is located downstream of Rac induces lamellipodia formation. These proteins are present at the leading edge of moving cells and generate driving force.
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Yamaguchi, H., Miki, H., Takenawa, T: "Neural Wiskott-Aldrich Syndrome Protein is involved in hepatocyte growth factor-induced migration, invasion, and tuboligenesis of epithelial cells"Cancer Res.. 62. 2503-2509 (2002)
Yamaguchi, H.、Miki, H.、Takenawa, T:“神经 Wiskott-Aldrich 综合征蛋白参与肝细胞生长因子诱导的上皮细胞迁移、侵袭和小管生成”Cancer Res.. 62. 2503-2509 (2002
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Otsuki, M., Itoh, T., Takenawa, T.: "N-WASP is recruited to rafts and associates with wndophilin A in response to EGF"J. Biol. Chem.. 278. 6461-6469 (2003)
Otsuki, M., Itoh, T., Takenawa, T.:“N-WASP 被募集到筏上并与亲细胞蛋白 A 结合以响应 EGF”J。
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Suetsugu,S., Hattori,M., Miki,H., Tezuka,T., Yamamoto,T., Mkoshima,K., Takenawa,T.: "Sustained Activation of N-WASP through Phosphorylation Is Essential for Neurite Extension"Dev.Cell. 3. 645-658 (2002)
Suetsugu,S.、Hattori,M.、Miki,H.、Tezuka,T.、Yamamoto,T.、Mkoshima,K.、Takenawa,T.:“通过磷酸化持续激活 N-WASP 对于神经突延伸至关重要”
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Suetsugu, S: "Requirement of the basic region of N-WASP/WAVE2 for actin-based motility"Biochem. Biophys. Res. Commun. 282. 739-744 (2001)
Suetsugu, S:“N-WASP/WAVE2 基本区域对于基于肌动蛋白的运动的要求”Biochem。
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Ijuin, T., Takenawa, T.: "SKIP Negatively Regulates Insulin-Induced GLUT4 Translocation and Membrane Ruffle Formation"Mol Cell Biol.. 23. 1209-1220 (2003)
Ijuin, T., Takenawa, T.:“SKIP 负向调节胰岛素诱导的 GLUT4 易位和膜皱褶形成”Mol Cell Biol.. 23. 1209-1220 (2003)
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共 14 条
Spatial and temporal regulation of signalling molecules by phosphoinositides
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批准号:18GS0312
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项目类别:Grant-in-Aid for Creative Scientific Research
-
资助金额:$280.55万
-
财政年份:2006
-
负责人:TAKENAWA Tadaomi
-
依托单位:
Migration of cancer cells and its regulatory mechanism
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批准号:17014018
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项目类别:Grant-in-Aid for Scientific Research on Priority Areas
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资助金额:$129.98万
-
财政年份:2005
-
负责人:TAKENAWA Tadaomi
-
依托单位:
Signaltransduction of cytoskeleton and cell movement
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批准号:12219202
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项目类别:Grant-in-Aid for Scientific Research on Priority Areas
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资助金额:$142.59万
-
财政年份:2000
-
负责人:TAKENAWA Tadaomi
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依托单位:
Attempt for regulating biologial activities by use of molecular recognition of SH2 and SH3 domains.
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批准号:07558091
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项目类别:Grant-in-Aid for Scientific Research (A)
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资助金额:$8.32万
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财政年份:1995
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负责人:TAKENAWA Tadaomi
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依托单位:
Role of PIP2 and PIP3 binding proteins on cell growth signals
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批准号:06404022
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项目类别:Grant-in-Aid for Scientific Research (A)
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资助金额:$18.69万
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财政年份:1994
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负责人:TAKENAWA Tadaomi
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依托单位:
Involvement of phosphatidylinositol 3-kinase in cell growth
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批准号:03454163
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$4.54万
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财政年份:1991
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负责人:TAKENAWA Tadaomi
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依托单位:
Phosphatidylinositol Kinase Activation Mechanism by Growth Factors
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批准号:01480160
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$3.84万
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财政年份:1989
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负责人:TAKENAWA Tadaomi
-
依托单位:
Regulation of phosphatidylinositol kinase activity
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批准号:62480454
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$3.52万
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财政年份:1987
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负责人:TAKENAWA Tadaomi
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依托单位:
Development of inositol 1,4,5-trisphosphate assay kit
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批准号:61870017
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项目类别:Grant-in-Aid for Developmental Scientific Research
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资助金额:$5.06万
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财政年份:1986
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负责人:TAKENAWA Tadaomi
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依托单位:
Role of polyphosphoinositide synthesizing enzyme in intracellar signal transduction system
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批准号:60480131
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$3.97万
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财政年份:1985
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负责人:TAKENAWA Tadaomi
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依托单位:
海外基金