Analysis of the machinery of ectodomain shedding and its possible role for the action of HB-EGF

分析胞外域脱落的机制及其对 HB-EGF 作用的可能作用

• 批准号: 22790319
• 负责人: FUKUDA Shinji
• 金额: $ 2.5万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790319/
• 关键词: 膜型増殖因子; ectodomain shedding; HB-EGF; Amphiregulin; アネキシン; ADAM17

We identified cell surface-annexins as components of their shedding complex. Annexin family members, annexin A2(ANXA2), A8, and A9 interacted with ADAM17 on the cell surface. Shedding of proHB-EGF was increased when ANXA2 was knocked down, but decreased with ANXA8 knockdown. Taken together with studies of its related ligand, Amphiregulin, we propose that annexins on the cell surface function as" shedding platform" proteins to determine the substrate selectivity of ADAM17, with possible therapeutic potential in ADAM-related diseases.

我们确定细胞表面膜联蛋白作为其脱落复合物的组成部分。膜联蛋白家族成员，膜联蛋白A2（ANXA 2），A8和A9与细胞表面上的ADAM 17相互作用。当ANXA 2被敲低时，proHB-EGF的脱落增加，但随着ANXA 8的敲低而减少。结合其相关配体双调蛋白的研究，我们提出细胞表面的膜联蛋白作为”脱落平台”蛋白来确定ADAM 17的底物选择性，在ADAM相关疾病中具有可能的治疗潜力。

项目成果

Monoubiquitination of pro-amphiregulin regulates its endocytosis and ectodomain shedding

• DOI: 10.1016/j.bbrc.2012.02.156
• 发表时间: 2012-04-06
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Fukuda, Shinji;Nishida-Fukuda, Hisayo;Higashiyama, Shigeki
• 通讯作者: Higashiyama, Shigeki

HB-EGF-CTF nuclear translocation induces gastric cancer invasion.

HB-EGF-CTF核易位诱导胃癌侵袭。

• 发表时间: 2010
• 作者: 藤田浩司;米田正人;志村貴也
• 通讯作者: 志村貴也

Identification of novel molecules that regulate ectodomain shedding of EGF ligands.シンポジウム" Ectodomain shedding biology-functional conversion of plasma membrane proteins"

调节 EGF 配体胞外域脱落的新分子的鉴定。研讨会“胞外域脱落生物学-质膜蛋白功能转换”

• 发表时间: 2010
• 作者: Fukuda S;Nakayama H;Higashiyama S
• 通讯作者: Higashiyama S

The Role of monoubiquitination in the regulation of endocytosis and ectodomain shedding of a ligand for epidermal growth factor(EGF) receptor, Amphiregulin

单泛素化在表皮生长因子 (EGF) 受体配体双调蛋白内吞作用和胞外域脱落调节中的作用

• 发表时间: 2011
• 作者: Fukuda S;Nishida-Fukuda H;Nakayama H;Inoue H;Higashiyama S
• 通讯作者: Higashiyama S

BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signaling in angiogenesis

• DOI: 10.1182/blood-2011-03-345306
• 发表时间: 2012-03-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Ohnuki, Hidetaka;Inoue, Hirofumi;Higashiyama, Shigeki
• 通讯作者: Higashiyama, Shigeki