Analysis of tyrosine kinase chimeric gene

酪氨酸激酶嵌合基因分析

• 批准号: 13671057
• 负责人: EMI Nobuhiko
• 金额: $ 1.79万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671057/
• 关键词: Leukemia; SYK; Tyrosine kinase; PDGFR; CEV; TEL; STAT5; PI3K

We here investigate the intracellular signal transduction of the stable transfectants. TEL-Syk fusion protein was associated with p85 subunit of phosphatidyl inositol 3 kinase (PI3-K) followed by the activation of Akt in the absence of IL-3. Vav, phospholipase C-γ2 (PLC-γ2) and mitogen-activated protein kinase (MAPK) were also constitutively activated. TEL-Syk also activated signal transducer and activator of transcription (STAT) 5 in the absence of Janus kinase 2 (JAK2) activation. None of these kinases were phosphorylated in the BaF3 cell transfected with TELΔPNT-Syk in which the oligomerization domain of TEL was deleted. Piceatannol, the Syk specific kinase inhibitor, inhibited the activation of STAT5 and the growth of the TEL-Syk transformed cell. These data suggest that TEL-Syk fusion protein in cytoplasm leads to constitutive activation of PI3-K, PLC-γ, MAPK and STAT5 signal pathways which are closely involved in IL-3 independent cell proliferation of BaF3 cells.

我们在这里调查的细胞内信号转导的稳定转染。TEL-Syk融合蛋白与磷脂酰肌醇3激酶（PI 3-K）的p85亚基相关，随后在不存在IL-3的情况下激活Akt。Vav、磷脂酶C-γ2（PLC-γ2）和丝裂原活化蛋白激酶（MAPK）也被组成性激活。TEL-Syk还在Janus激酶2（JAK 2）激活不存在的情况下激活信号转导子和转录激活子（STAT）5。在缺失TEL寡聚化结构域的TELΔPNT-Syk转染的BaF 3细胞中，这些激酶均未被磷酸化。Syk特异性激酶抑制剂Piceatannol可抑制STAT 5的活化和TEL-Syk转化细胞的生长。这些数据表明，胞浆中的TEL-Syk融合蛋白导致PI 3-K、PLC-γ、MAPK和STAT 5信号通路的组成性激活，这些信号通路与BaF 3细胞的IL-3非依赖性细胞增殖密切相关。

项目成果

KUNO Yoshie et al.: "Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12) (q22;p12)"BLOOD. 97. 1050-1055 (2001)

KUNO Yoshie 等人：“t(9;12) (q22;p12) 骨髓增生异常综合征中 TEL-Syk 融合基因的组成型激酶激活”BLOOD。

Eiki Kanbe, Akihiro Abe, Masayuki Towatari, Hidehiko Saito, Nobuhiko Emi: "DR1-like Element in Human Topoisomerase IIa Gene involved in Enhancement of Etoposide-induced Apoptosis by PPARg ligand"Experimantal hematology. (in press).

Eiki Kanbe、Akihiro Abe、Masayuki Towatari、Hidehiko Saito、Nobuhiko Emi：“人类拓扑异构酶 IIa 基因中的 DR1 样元件参与 PPARg 配体增强依托泊苷诱导的细胞凋亡”实验血液学。

KOHNO Akio, TSUZUKI Shinobu, KASAI Masanobu, MIYAMURA Koichi, EMI Nobuhiko, TANIMOTO Mitsune, SAITO Hidehiko: "Acute Promyelocytic Leukemia with Apparently Normal Karyotype : Molecular Findings and Response to All-Trans Retinoic Acid"Leukemia and Lymphoma

KOHNO Akio、TSUZUKI Shinobu、KASAI Masanobu、MIYAMURA Koichi、EMI Nobuhiko、TANIMOTO Mitsune、SAITO Hidehiko：“具有明显正常核型的急性早幼粒细胞白血病：分子发现和对全反式视黄酸的反应”白血病和淋巴瘤

KANBE Eiki, EMI Nobuhiko, ABE Akihiro, TANAKA Hidehiko, KOBAYASHI Kazukiyo, SAITO Hidehiko: "Novel Synthesized Trimannose Conjugate Induces Endocytosis and Expression of Immunostimulatory Molecules in Monocytic Leukemia Cells"International Journal of HEMA

KANBE Eiki、EMI Nobuhiko、ABE Akihiro、TANAKA Hidehiko、KOBAYASHI Kazukiyo、SAITO Hidehiko：“新型合成三甘露糖缀合物在单核细胞白血病细胞中诱导内吞作用和免疫刺激分子的表达”International Journal of HEMA

KUNO Yoshie, ABE Akihiro, EMI Nobuhiko, IIDA Minako, YOKOZAWA Toshiya, TOWATARI Masayuki, TANIMOTO Mitsune, SAITO Hidehiko: "Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t (9 ; 12) (q22 ; p12)"BLOOD. 97. 1050-

KUNO Yoshie、ABE Akihiro、EMI Nobuhiko、IIDA Minako、YOKOZAWA Toshiya、TOWATARI Masayuki、TANIMOTO Mitsune、SAITO Hidehiko：“骨髓增生异常综合征中 TEL-Syk 融合基因的组成型激酶激活（9；12）（q22；p12）