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是其脱落复合物的组成部分。膜联蛋白家族成员膜联蛋白 A2(ANXA2)、A8 和 A9 与细胞表面的 ADAM17 相互作用。当ANXA2被敲低时，proHB-EGF的脱落增加，但当ANXA8敲低时，proHB-EGF的脱落减少。结合对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 ADAM17 的底物选择性，在 ADAM 相关疾病中具有潜在的治疗潜力。

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

Amphiregulin nuclear translocation might cause poor prognosis due to chemotherapeutic resistance in gastric cancer

双调蛋白核易位可能因胃癌化疗耐药而导致预后不良

• 发表时间: 2011
• 作者: Yoshida M;Shimura T;Fukuda S;Higashiyama S;Mizoshita T;Kataoka H;Joh T
• 通讯作者: Joh T

ZNF689 suppresses apoptosis of hepatocellular carcinoma through the down-regulation of Bcl-2 family members

ZNF689通过下调Bcl-2家族成员抑制肝细胞癌凋亡

• 发表时间: 2011
• 作者: Shigematsu S;Hiasa Y;Fukuda S;Nakayama H;Onji M;Higashiyama S
• 通讯作者: Higashiyama S

Ectodomain shedding and remnant peptide signalling of EGFRs and their ligands

• DOI: 10.1093/jb/mvr068
• 发表时间: 2011-07-01
• 期刊: JOURNAL OF BIOCHEMISTRY
• 影响因子: 2.7
• 作者: Higashiyama, Shigeki;Nanba, Daisuke;Fukuda, Shinji
• 通讯作者: Fukuda, Shinji

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