Regulation of KIF3 motor by dephosphorylation

通过去磷酸化调节 KIF3 马达

• 批准号: 22590298
• 负责人: SHIMA Hiroshi
• 金额: $ 2.83万
• 依托单位: Miyagi Cancer Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590298/
• 关键词: 分子腫瘍学; キネシンモーター; KIF3; ホスファターゼ; ２重基質ホスファターゼ; 2重基質ホスファターゼ; 2重基質ボスファターゼ; 癌

We identified the protein-phosphatase DUSP26 as a novel regulator of the KIF3 motor. Dusp26 is recruited to the KIF3 motor mainly by interaction with Kif3a, and thereby dephosphorylates Kap3. Enzyme activity of the Dusp26 was shown to promote distribution of beta-catenin/N-cadherinto cell-cell junction sites, resulting in increased cell-cell adhesiveness. We also showed that DUSP26 mRNA expression was downregulated in human glioblastoma samples, and a CpG island upstream of the DUSP26 transcrptional start site was heavily methylated in glioma cell lines. These results suggest previously unidentified functions of DUSP26 in intracellular transport and cell-cell adhesion.Downregulation of DUSP26 may contribute to malignant phenotypes of glioma. We showed that DUSP13B inactivated MAPK activation in the order of selectivity, JNK=p38> ERK in cells. Reporter gene analysis showed that DUSP13B had significant inhibitory effect on AP-1 dependent gene expression. DUSP13B is the first identified testis specific phosphatase that inhibits stress-activated MAPKs.

我们发现蛋白磷酸酶DUSP26是KIF3马达的一种新的调节因子。Dusp26主要通过与Kif3a的相互作用被募集到KIF3马达中，从而使Kap3去磷酸化。Dusp26的酶活性可促进β -catenin/ n -cadherin在细胞-细胞连接位点的分布，从而增加细胞-细胞的粘附性。我们还发现DUSP26 mRNA在人类胶质母细胞瘤样本中表达下调，并且在胶质瘤细胞系中DUSP26转录起始位点上游的CpG岛被严重甲基化。这些结果表明DUSP26在细胞内运输和细胞-细胞粘附中的功能是以前未被发现的。DUSP26的下调可能与胶质瘤的恶性表型有关。我们发现DUSP13B按选择性顺序使MAPK失活，细胞中JNK=p38 bb0 ERK。报告基因分析显示，DUSP13B对AP-1依赖性基因表达有显著抑制作用。DUSP13B是第一个发现的睾丸特异性磷酸酶，可以抑制应激激活的MAPKs。

项目成果

The phosphatase interactor NIPP1 regulates the occupancy of the histone methyltransferase EZH2 at Polycomb targets.

• DOI: 10.1093/nar/gkq643
• 发表时间: 2010-11
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Van Dessel N;Beke L;Görnemann J;Minnebo N;Beullens M;Tanuma N;Shima H;Van Eynde A;Bollen M
• 通讯作者: Bollen M

MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm

• DOI: 10.1016/j.bbrc.2010.01.097
• 发表时间: 2010-03-05
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Masuda, Kouhei;Katagiri, Chiaki;Shima, Hiroshi
• 通讯作者: Shima, Hiroshi

Conversion of pyruvate kinase M (PKM) isozymes in human canters-an analysis using isoform-specific antibodies

人体内丙酮酸激酶 M (PKM) 同工酶的转化 - 使用同工型特异性抗体进行分析

• 发表时间: 2010
• 作者: Yoshimitsu M;Higuchi K;Miyata M;Devine S;Mattman A;Sirrs S;Medin JA;Tei C;Takenaka T;島礼
• 通讯作者: 島礼

Sialidase NEU4 Hydrolyzes PolysialicAcids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons J.Biol.Chem.

唾液酸酶 NEU4 水解神经细胞粘附分子的聚唾液酸并负调节海马神经元的神经突形成 J.Biol.Chem。

• 发表时间: 2012
• 期刊: J.Biol.Chem.
• 作者: Takahashi K;Mitoma J;Hosono M;Shiozaki K;Sato C;Yamaguchi K;Kitajima K;Higashi H;Nitta K;Shima H;and Miyagi T
• 通讯作者: and Miyagi T

Analysis of Protein Phosphatases in Human Glioma Samples

人类神经胶质瘤样品中蛋白磷酸酶的分析

• 发表时间: 2011
• 作者: Pacienza N;Yoshimitsu M;Mizue N;Au BCY;Wang JCM;Fan X;Takenaka T;Medin JA;Tamiya G;Shima H
• 通讯作者: Shima H