Significance and functional analysis of protein-tyrosine phosphatases expressed in hematopoietic disorders.

造血障碍中表达的蛋白酪氨酸磷酸酶的意义和功能分析。

• 批准号: 05807096
• 负责人: ADACHI Masaaki
• 金额: $ 1.22万
• 依托单位: Sapporo Medical University School of Midicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05807096/
• 关键词: Protein-tyrosine phosphatase; LC-PTP; SHPTP2; IL-2; Chromosome assignment; genome DNA; tyrosine kinase; 染色体マップ; 分子生物学

Protein-tyrosine phosphatases (PTPs) are known to play a role in removal of phosphate groups from phosphotyrosines, which accumulate after activation of tyrosine kinases. We have already isolated cDNAs encoding PTPs expressed in hematopoietic cells. Here, we investigate the abnormalities of their genomic structures and expressions to see the correlation of PTPs with oncogenesis. We obtained the results as described below.We isolated LC-PTP genomic clones and demonstrated the genomic organization. LC-PTP gene consists of 11 exons and its organizations are similar to CD45 gene (transmembrane PTP). From this study, we can analyze the somatic mutations in LC-PTP gene by PCR method.We found LC-PTP gene expression is induced by IL-2 stimulation, and demonstrated that LC-PTP gene is an early response gene. This data suggests that LC-PTP can function in T-cell proliferation.We have mapped SH-PTP gene. SH-PTP gene is localized at chromosome 12q24.1 This locus is knowm to be associated with chromosomal abnormalities in chronic lymphocytic leukemia (CLL), germ cell tumors, and leiomyoma. It is of interest that functional analyzes of SH-PTP2 in the disorders.We generated polyclonal antibody to SH-PTP2, and see localization of SHPTP2 expressions. We found SHPTP2 is highly expressed in vascular smooth muscle cells ubiquitously. We are investigating SHPTP2 functions in cardiovascular system.

蛋白酪氨酸磷酸酶(PTPs)在酪氨酸激酶激活后积累的磷酸酪氨酸中起着清除磷酸基团的作用。我们已经分离了编码在造血细胞中表达的PTP的cDNA。在这里，我们调查它们的基因组结构和表达的异常，以了解PTPs与肿瘤发生的相关性。我们获得了如下结果。我们分离了LC-PTP基因组克隆，并证明了其基因组结构。LC-PTP基因由11个外显子组成，其组织结构类似于CD45基因(跨膜型PTP)。通过本研究，我们可以对LC-PTP基因的体细胞突变进行分析，发现LC-PTP基因的表达是由IL-2刺激诱导的，证明LC-PTP基因是一个早期反应基因。这说明LC-PTP在T细胞增殖中具有一定的功能。SH-PTP基因定位于染色体12q24.1，该基因与慢性淋巴细胞白血病(CLL)、生殖细胞肿瘤和子宫肌瘤的染色体异常有关。我们制备了针对SH-PTP2的多克隆抗体，并观察了SHPTP2表达的定位。我们发现SHPTP2在血管平滑肌细胞中普遍高表达。我们正在研究SHPTP2在心血管系统中的功能。

项目成果

F.Itoh, et al.: "Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal-associated proteins." Int.J.Cancer. 55. 947-951 (1993)

F.Itoh 等人：“编码与细胞骨架相关蛋白同源的胞浆蛋白酪氨酸磷酸酶的 PTPH1 基因的表达和染色体分配。”

Masaaki Adachi: "Induction of protein-tyrosine phosphatase LC-PTP by IL-2 in human T cells-LC-PTP is an early response gene-." FFBS Lett.338. 47-52 (1994)

Masaaki Adachi：“人类 T 细胞中 IL-2 诱导蛋白酪氨酸磷酸酶 LC-PTP -LC-PTP 是一种早期反应基因 -”。

Mutsuhiro Takekawa: "Chromosomal localization of protein tyrosine phosphatase G1 gene and characteri-zation of the aberrant transcripts in human colon cancercells." FEBS Letters. (in press).

Mutsuhiro Takekawa：“蛋白质酪氨酸磷酸酶 G1 基因的染色体定位和人类结肠癌细胞中异常转录本的表征。”

Hiroshi Maegawa: "Insulin receptor kinase phosphorylates protein tyrosine phosphatase containing Src homology regions and modulates its PTPase activity in vitro." Biochem.Biophys.Res.Commun.199. 780-785 (1994)

Hiroshi Maekawa：“胰岛素受体激酶磷酸化含有 Src 同源区域的蛋白酪氨酸磷酸酶，并在体外调节其 PTPase 活性。”

Masaaki Adachi: "Structure of the human LC-PTP(HePTP)gene:similarity in genomic organization within protein-tyrosine phosphatase genes." Oncogene. 9. 3031-3035 (1994)

Masaaki Adachi：“人类 LC-PTP（HePTP）基因的结构：蛋白质酪氨酸磷酸酶基因内基因组组织的相似性。”