Cloning of Seel-renewal factor receptors from hemopoietic stem cells

造血干细胞 Seel 更新因子受体的克隆

• 批准号: 05454333
• 负责人: SUDA Toshio
• 金额: $ 4.35万
• 依托单位: Kumamoto University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 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-05454333/
• 关键词: Hematopoietic Stem Cells; Endothelial cells; STK; RON; MSP; TIE; TEK; Reccptor tyrosine kinases; FACS; TIE遺伝子; TEK遺伝子; RON遺伝子

Receptor and cytoplasmic tyrosine kinases essential functions in the hematopoietic cell development and signal transduction. In this project, we have characterized novel receptor tyrosine kinases, STK and TIE which are expresed in hematopoietic cells.STK encodes a 1,378 amino acid protein. STK was expressed in a various stage of hematopoietic cells including cells, but ont apparent expression in other adult tissues. We recently confirmed that STK prtein was phosphorylated by the binding of macrophage stimulating factor (MSP) of HGF-like protein (HLP) . As is the case in HGF/c-MET system, MSP/STK system is functional in hematopoietic cells. We have shown that MSP/STK play a role in the differentiation of macrophages and erythroid cells.TIE is unclassified RTK which is expressed in megakaryocytes and stem cells as well as endothelial cells. The amino acid homology between murine TIE and TEK was 46.2% in total. They shared a unique structural prperty of coexistent immunoglobulin-like domain, epidermal growth factor-like repeats, and fibronectin type lll repeats in their extracellular domains. The mouse TIE and TEK genes are located very close in chromosome4. This is syntenic to human chromosome region, 1p34 and 9p21, where the human TIE and TEK gene are mapped, respectively. Thus, TIE and TEK are tow linked members of a gene. Flow cytomery shows that TIE is mainly expressed in the fraction of CD34-positive of c-kit-positive cells. lt is interesting that TIE and TEK are expressed in both endothelial cells and hematopoietic stem cells, since both cells are thought to originate from the same progenitor cells. We hope that characterization of these kinases will be helpful to elucidate the molecular mechanism of the growth regulation of hematopoietic stem cells.

受体和胞质酪氨酸激酶在造血细胞发育和信号转导中起重要作用。本研究中，我们鉴定了在造血细胞中表达的新型受体酪氨酸激酶STK和TIE，STK编码一个1,378个氨基酸的蛋白。STK在包括细胞在内的各期造血细胞中均有表达，但在其它成体组织中无明显表达。我们最近证实，STK蛋白通过与HGF样蛋白（HLP）的巨噬细胞刺激因子（MSP）结合而磷酸化。与HGF/c-MET系统的情况一样，MSP/STK系统在造血细胞中具有功能。我们已经发现MSP/STK在巨噬细胞和红系细胞的分化中起作用，TIE是未分类的RTK，其在巨核细胞和干细胞以及内皮细胞中表达。小鼠TIE与TEK的氨基酸同源性为46.2%。它们的细胞外结构域中存在免疫球蛋白样结构域、表皮生长因子样重复序列和纤连蛋白III型重复序列。小鼠TIE和TEK基因位于非常接近的染色体4。这与人类染色体区域1 p34和9 p21同线，其中分别定位了人类TIE和TEK基因。因此，TIE和TEK是一个基因的两个连锁成员。流式细胞术显示TIE主要表达于c-kit阳性细胞中的CD 34阳性细胞。有趣的是，TIE和TEK在内皮细胞和造血干细胞中都表达，因为这两种细胞被认为起源于相同的祖细胞。我们希望这些激酶的特性将有助于阐明造血干细胞生长调节的分子机制。

项目成果

Gunji Y et al: "Human primitive hemopoietic progenitor cells are more enriched in KIT^<low> cells than KIT^<high> cells" Blood. 82. 3283-3289 (1993)

Gunji Y 等人：“人类原始造血祖细胞中 KIT^<低> 细胞比 KIT^<高> 细胞更丰富” 血液。

Muroi K et all: "Expression of sialyl-Lewis^x in CD34-positivel eukemic blasts" Leukemia. 7. 336-337 (1993)

Muroi K 等人：“CD34 阳性白血病细胞中唾液酸-Lewis^x 的表达”白血病。

lwama A et al: "Molecular cloning of a novel receptor tyrosine kinase gene, STK,derived from enriched hematopoietic stem cells" Blood. 83. 3160-3169 (1994)

lwama A 等人：“源自富集造血干细胞的新型受体酪氨酸激酶基因 STK 的分子克隆”血液。

Sakano Set al: "Molecular cloning of a novel non-receptor tyrosine kinase, HYL (hematopoietic concersus tyrosine-lacking kinase)" Oncogene. 9. 1155-1161 (1994)

Sakano Set al：“新型非受体酪氨酸激酶 HYL（造血细胞酪氨酸缺乏激酶）的分子克隆”癌基因。

Sakamoto O: "Interleukin-13 selectively suppress the growth of human macrophage progenitors at the late stage" Blood. in press. (1995)

坂本O：“白细胞介素13选择性地抑制晚期人类巨噬细胞祖细胞的生长”血液。